Passive Monoclonal and Polyclonal Antibody Therapies

Passive Polyclonal Antibodies Therapy

Passive Polyclonal Antibody Treatment Overview

Polyclonal immunoglobulins have been in use since the 19th century to protect against infectious agents, toxins, and disease conditions such as those with an autoimmune etiology. These immunoglobulin preparations are made from pools of selected human donors or animals with high titers of antibodies against viruses and toxins. These antibody treatments provide passive transfer of high titer antibodies that either reduces risk or reduces severity of infection. They are used to prevent hemolytic disease of the newborn and modify inflammatory reactions. Earlier drugs were very nonselective and patients frequently succumbed to infection due to suppression of both antibody-mediated (humoral) and cell-mediated arms of the immune system. Today, the principal approach is to alter lymphocyte function using drugs or antibodies against immune proteins. However, with the advent of human organ and tissue transplantation (e.g., kidney, heart, bone marrow, and/or peripheral blood stem cells) as treatment options, these polyclonal antibody therapies in combination with other treatment regimens are being used to lower the ability of the body's immune system to reject these transplants. However, their use is not without risk, as complications include development of immune complexes and severe allergic reactions. A summary of these polyclonal antibody therapies may be found in Table 16.2.

Immunosuppressive Agents: Disease Modifying

Antithymocyte globulin (rabbit)/thymoglobulin; antithymocyte globulin (equine)/Atgam

Description

Rabbit antithymocyte globulin (rATG) and equine antithymocyte globulin (eATG) are purified, pasteurized preparation of lymphocyte depleting polyclonal gamma immunoglobulin (IgG) raised against human thymus lymphocytes in rabbits and horses, respectively. They are used in prevention and/or treatment of renal transplant rejection worldwide. 1 , 2 , 3 , 4 , 5 , 6 , 7

History of antibody use

rATG induction in combination with immunosuppressive therapy is more effective in preventing episodes of acute renal graft rejection in adult renal transplant recipients, in recurrent episodes of acute rejection, 8 , 9 and those acute rejections that are not responsive to high-dose corticosteroid therapy than other monoclonal antibody preparations. 10 , 11 rATG recipients had a lower incidence of biopsy-confirmed acute rejection episodes, 12 greater event-free survival up to 10 years posttransplantation, and greater graft survival up to 5 years posttransplantation. 13

Mechanisms of action

The exact mechanism of these polyclonal antibodies has not been fully understood. 3 , 4 , 14 , 15 , 16 , 17 , 18 , 19 , 20 However, being polyclonal, they display specificity toward a wide variety of surface antigens (Ags) expressed on T and B-lymphocytes, dendritic cells, natural killer (NK) cells, and endothelial cells. However, T-cell depletion is considered to play a key role by modulating the expression of lymphocyte surface antigens involved in a wide variety of functions such as T-cell activation to endothelial adherence, activation of certain transcription factors, and interference with numerous immune cell processes, such as cytokine production, chemotaxis, endocytosis, cell stimulation, and proliferation. 14 , 15 , 16 , 17 , 18 , 19 , 20

In vitro studies indicate that binding of eATG to cells is generally nonspecific; the drug binds to visceral tissues, including thymus and testis cell membranes and nuclear and cytoplasmic components of tissues such as tonsil, kidney, and liver, 21 and is extensively bound to bone marrow cells, 22 and to other peripheral blood cells besides lymphocytes. 21

Diseases treated

As mentioned earlier, both antithymocyte globulins are used for treatment and prevention of acute renal allograft rejection. 2 , 3 , 4 , 5 , 6 , 7 , 8 More rATG recipients have been reported to achieve the endpoint of successful response (return of serum creatinine levels to baseline by end of treatment or within 14 days of treatment initiation). However, among those who achieved a successful response, fewer episodes of recurrent rejection occurred with rATG within 90 days of treatment cessation. 2 eATG is also used for treating moderate-to-severe aplastic anemia in patients who are unsuitable for bone marrow transplantation. 3 , 23 , 24

Adverse effects

The most common adverse effects are fever, thrombocytopenia, leukopenia, gastrointestinal disorders, and/or concurrent infection. 1 , 2 Cytomegalovirus (CMV) infection was generally higher with rATG except in high-risk patients. 1 , 25 eATG therapy may result in reactivation of or infection with CMV, herpes simplex virus, 25 or Epstein–Barr virus. 26 The incidence of malignancies is generally lower with rATG therapy. 27 This product is made of equine and human blood components, so it may carry a risk of transmitting infectious agents such as viruses, and theoretically, the Creutzfeldt–Jakob disease (CJD) agent.

Update

There has been recent evidence that the addition of human anti-T-lymphocyte globulin (ATLG) plus cyclosporine and methotrexate to standard graft-versus-host disease (GVHD) prophylaxis is preferred over standard GVHD prophylaxis alone because it improves the probability of survival without relapse and of chronic GVHD after myeloablative peripheral blood stem-cell transplantation from a human leukocyte antigen (HLA)-identical sibling donor for patients with acute leukemia in remission. Additionally, this therapy provides better quality of life and shorter immunosuppressive treatment compared to standard GVHD prophylaxis without ATLG. 22

Antitoxin and Immune Globulins: Disease Modifying

Tetanus immune globulin/Baytet/Hypertet

Description

Tetanus immune globulin (TIG) is a specific solvent-detergent-treated plasma-derived product obtained from donors immunized with tetanus toxoid. TIG contains tetanus antitoxin that provides temporary passive immunity to individuals who have low or no immunity to the toxin produced by Clostridium tetani . 28 , 29

Mechanisms of action

TIG contains tetanus antitoxin antibodies, which neutralize the free form of the powerful exotoxin produced by Clostridium tetani . 28 , 30 TIG can only neutralize unbound exotoxin; it does not affect toxin already bound to nerve endings. 31

Diseases treated

TIG is used to provide passive immunity to tetanus as part of a postexposure prophylaxis regimen following an injury in patients whose immunization is incomplete or uncertain or if it has been more than 10 years since last dose of tetanus toxoid. 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9

Adverse reaction

Slight soreness at injection site, mild fever, and rarely sensitization to repeated injections of human immune globulin has been reported. 28

Antitoxin and Immune Globulins: Disease Modifying

Cytomegalovirus immune Globulin/Cytogam

Description

Cytomegalovirus immune globulin IV (CMV-IG) is a purified immune globulin (hyperimmune globulin) that contains immunoglobulin G (IgG) derived from pooled adult human plasma selected for high titers of anti-CMV antibodies. 32

Mechanisms of action

CMV-IG provides relatively high concentration of antibodies directed against CMV. It provides prophylaxis against CMV infection or disease in immunocompromised individuals. 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 Results from in vitro studies and mice indicate that anti-CMV antibodies can neutralize the pathogenic properties of CMV. 42 , 43 , 44 As CMV usually targets a population of bone marrow-derived myeloid lineage progenitor cells, antibody-neutralization of the virus alone may not be enough to prevent or make active disease less severe in already CMV-infected individuals. 42 , 44 , 45 , 46 , 47

Disease treated

CMV-IG provides passive immunity to individuals who are at risk for primary CMV infection/disease, or secondary CMV disease (reactivation of CMV). 41 , 42 , 44 , 45 , 46 , 48 , 49 , 50 , 51 It is also prescribed for the prophylaxis of CMV disease associated with transplantation of kidney, lung, liver, pancreas, and heart. With the exception of CMV-seronegative recipients of kidneys from CMV-seropositive donors, CMV-IG prophylaxis should be considered in conjunction with ganciclovir.

Adverse reactions

Most frequent adverse reactions reported are flushing, chills, muscle cramps, back pain, fever, nausea, vomiting, arthralgia, and wheezing. 32 , 34 , 35 , 36 There is a slight risk of hemolysis, as intravenous immunoglobulin (IVIG) products can contain blood group antibodies, which may act as a hemolysin and induce in vivo coating of red blood cells with immunoglobulin, causing a positive direct antiglobulin reaction. Transfusion-related acute lung injury (noncardiogenic pulmonary edema) and thrombotic events have been reported in patients receiving IVIG preparations. 32

Similar to all other products made from human plasma, this CMV-IG also carries the possibility for transmission of blood-borne viral agents and the CJD agent. However, this IVIG is treated with a solvent detergent viral inactivation procedure to inactivate a wide spectrum of lipid-enveloped viruses, including HIV-1, HIV-2, Hepatitis B, and Hepatitis C.

Antivenin [ latrodectus mactans ]/black widow spider antivenin—antivenin Micrurus fulvius /eastern and Texas coral snake antivenin—crotalidae polyvalent immune Fab/Crofab

Description

These antivenins are sterile, nonpyrogenic, purified, and lyophilized preparation of specific venom-neutralizing serum globulins obtained from the blood serum of healthy horses exposed to the venom of black widow spiders and eastern coral snake ( Micrurus fulvius ) venom, respectively. 52 , 53 , 54 , 55 In contrast, crofab is an antivenin made up of ovine Fab (monovalent) immunoglobulin fragments obtained from blood of healthy sheep immunized with North American Crotalinae subfamily of venomous snakes that includes rattlesnakes, copperheads, cottonmouth, or water moccasins. 56

Mechanisms of action

Mode of action of these antivenins is unknown. 52 However, they probably act by neutralizing venom of black widow spiders and coral snakes. 54 Crofab is a venom-specific Fab fragment of IgG that works by binding and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body. 56

Disease treated

These antivenins are indicated for patients with symptoms due to bites by black widow spider ( Latrodectus mactans ) 52 and bites of two genera of coral snakes, that is, Micrurus (including the eastern and Texas varieties) and Micruroides (the Sonoran or Arizona variety), found in southeastern Arizona and southwestern New Mexico. 52 , 57 , 58 , 59 Antivenin Micrurus fulvius (equine origin) is indicated only for treatment and management of adult and pediatric patients exposed to North American crotalid envenomation. 54

Adverse effects

Immediate systemic reactions (allergic reactions or anaphylaxis) and death can occur in patients sensitive to antivenin from horse serum. 52 , 60 Most common adverse reactions to crofab are urticaria, rash, nausea, pruritus, and back pain. 61 , 62

High antibody titer influenza fresh frozen plasma

Description

Use of convalescent (persons who have recovered from a particular infection) donor plasma with high hemagglutination inhibition titer against certain influenza strains has been recommended as a primary therapy for severe respiratory infectious diseases including influenza, severe acute respiratory syndrome, and Middle East respiratory syndrome. 63

History of antibody use

A meta-analysis of previous cohort studies during the 1918 influenza pandemic showed a case-fatality rate of 16% among subjects treated with plasma, serum, or whole blood compared to 37% among controls. Similarly, in 2009, a cohort study using convalescent plasma for the treatment of pandemic H1N1 influenza resulted in a mortality of 20% in the treatment group versus 54% in the control group. 64

Mechanisms of action

Antiinfluenza convalescent plasma decreases the rate of viral shedding measured by neutralizing antibody titer and hemagglutination inhibition. 65 Both preexisting immunity (previous infections and vaccinations) as well as any immune response occurring after illness onset makes this mechanism of action more complex.

Disease classifications treated

Influenza, severe acute respiratory syndrome, and Middle East respiratory syndrome. 63

Adverse effects

Convalescent plasma seems safe. The serious adverse events reported are related to the underlying influenza, its complications, preexisting comorbidities, and not due to the convalescent plasma usage.

High antibody titer ebola fresh frozen plasma

Description

Antibodies to the Ebola virus (EV) in whole blood or plasma from convalescent donors may be effective in the treatment of EV infection.

History of antibody use

The World Health Organization (WHO) has stated that convalescent blood or plasma is an option in the treatment of Ebola. 66 In 1999, transfusion of locally collected convalescent blood helped to decrease Ebola mortality. 67 Therefore, WHO has recommended the collection of convalescent plasma to treat patients with Ebola virus infection.

Mechanisms of action

This fresh frozen plasma (FFP) has high titers of antibodies directed against Ebola virus. 68

Adverse effects

Convalescent plasma seems safe with few adverse effects. 69 , 70

Digoxin immune Fab/DigiFab; Digibind

Description

Digoxin immune Fab is a sterile, purified, lyophilized monovalent preparation of bovine immunoglobulin Fab fragments that binds to digoxin. These Fab fragments are obtained from the blood of healthy sheep immunized with a digoxin derivative, digoxindicarboxymethoxylamine, a digoxin analogue that contains the functionally essential cyclopentaperhydrophenanthrene: lactone ring moiety coupled to keyhole limpet hemocyanin. The final product is prepared by taking the immunoglobulin fraction of the ovine serum, digesting it with papain, and isolating the digoxin-specific Fab fragments by affinity chromatography. 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79

Mechanisms of action

DigiFab or Digibind have antigen-binding fragments that bind to free digoxin molecules that results in an equilibrium shift away from binding to receptors, thereby reversing the cardiotoxic effects of the glycoside. 71 , 72 , 75 , 76 , 78 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 Subsequently, Fab-digoxin complexes are cleared by the kidney and reticuloendothelial system. Due to papain treatment, the Fab fragments lack the antigenic determinants of the Fc fragment resulting in reduced immunogenicity to patients as opposed to intact immunoglobulin products. 71 , 72 , 75 , 76 , 78 , 79 , 84 , 88 , 89

Diseases treated

Digoxin immune Fab is indicated for patients with either life-threatening or potentially life-threatening digoxin toxicity or overdose. 71 , 79 , 90 , 91 , 92 , 93 , 94 , 95 Data from clinical trials have showed that both DigiFab and Digibind reduce levels of free digoxin in the serum to below the limit of assay quantitation for several hours after Fab administration.

Adverse reactions

Digoxin immune Fab (ovine) generally is well tolerated following intravenous (IV) administration. 71 , 72 , 73 , 76 , 78 Hypokalemia may occur, sometimes developing rapidly in patients receiving digoxin immune Fab (ovine). 71 , 72 , 79 , 96 , 97 DigiFab should not be administered to patients with a known history of hypersensitivity to papaya or papain unless the benefits outweigh the risks.

Immune Globulins: Antiinfectious

Hepatitis B immune globulin/HepaGam B/nabi-HB/BayHepB/HyperHEP B S/D

Description

Hepatitis B immune globulin (HBIG) is a specific immune globulin (hyperimmune globulin) that contains antibody to hepatitis B surface antigen (anti-HBs) prepared from plasma of healthy donors with high titer (>1:100,000) of anti-HBs antibody. It provides temporary passive immunity against hepatitis B virus (HBV). 98 , 99 , 100 , 101 , 102 , 103 , 104

HepaGam-B is a solvent/detergent-treated sterile solution of purified gamma globulin containing antibody to HBs antigen that contains high titers of anti-HBs from plasma donated by healthy screened donors. Both HBIG and HepaGam-B are manufactured by a solvent/detergent (S/D) treatment procedure that is effective in inactivating lipid-enveloped viruses such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1 and type 2. However, S/D is less effective against nonlipid-enveloped viruses such as hepatitis A virus and parvovirus B-19. 100 , 101 , 104

Mechanisms of action

It provides passive immunization for individuals exposed to the hepatitis B virus by binding to the surface antigen and reducing rate of hepatitis B infection.

Diseases treated

HBIG provides passive prophylactic immunity to HBV infection for prevention of perinatal HBV infection in neonates born to HBs antigen-positive (HBsAg-positive) mothers, 100 , 101 , 102 , 103 , 104 , 105 , 106 for postexposure prophylaxis in susceptible individuals exposed to HBV or HBsAg-positive materials (e.g., blood, plasma, serum), 100 , 101 , 102 , 103 , 104 , 107 , 108 , 109 sexual exposure to HBsAg-positive persons, for household exposure to persons with acute HBV infection, and for prevention of HBV recurrence in liver transplant recipients who are HBsAg-positive (HepaGam-B only). 104 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 HBIG is not indicated for treatment of active hepatitis B infection and is ineffective in the treatment of chronic active hepatitis B infection. 105

Adverse reactions

The local adverse reactions that may occur at the site of injection after intramuscular (IM) administration are pain, tenderness, swelling, and erythema. 100 , 101 , 109 The systemic effects that may occur after IM administration are urticaria, angioedema, nausea, vomiting, myalgia, headache, flu- or cold-like symptoms, lightheadedness, and malaise have been reported. 100 , 101 , 104

Varicella zoster immune globulin/VariZIG

Summary

Varicella zoster immune globulin (VZIG) is a specific immune globulin (hyperimmune globulin). VZIG is prepared from plasma of donors selected for high titers of antibodies to varicella zoster virus (anti-VZV) and used to provide temporary passive immunity against VZV. 118 , 119 , 120

Mechanisms of action

VZIG acts by neutralizing varicella zoster virus via high titers of IgG antibodies present in the plasma used.

Diseases treated

VZIG is used for postexposure prophylaxis of varicella (chickenpox) in individuals who do not have evidence of varicella immunity and are at high risk for severe varicella infection and its complications. These high risk individuals include immunocompromised patients such as neonates whose mothers have signs and symptoms of varicella around the time of delivery (i.e., 5 days before to 2 days after), premature infants born at ≥28 weeks of gestation who are exposed during the neonatal period and whose mothers do not have evidence of immunity, premature infants born at <28 weeks of gestation or who weigh ≤1000 g at birth and were exposed during the neonatal period regardless of their mothers' evidence of immunity status, and finally pregnant women. 118 , 119 , 121 , 122

VZIG is now recommended for outbreak control and postexposure treatment, and the vaccine is available to children with humoral immunodeficiencies and selected children with HIV infection. 122 Use of VZIG for postexposure prophylaxis in pregnant women exposed to VZV may prevent or reduce severity of varicella in the woman but does not prevent fetal infection. 119 , 121

VZIG is not indicated for individuals who previously received age-appropriate varicella vaccination and subsequently became immunocompromised because of disease or immunosuppressive therapy later in life. Bone marrow transplant recipients should be considered susceptible to varicella regardless of previous history of varicella or varicella vaccination in themselves or their donors. However, those who develop varicella or herpes zoster after transplantation should be considered immune to varicella. 119

Adverse reactions

The most common adverse effects reported with VZIG in clinical trials in pregnant women, infants, and immunocompromised adults and children were injection site pain, headache, chills, fatigue, rash, and nausea. Severe hypersensitivity reactions may occur following administration of VZIG. 118

Rimabotulinumtoxin B/Myobloc

Summary

Rimabotulinumtoxin B, a type B botulinum toxin produced by fermentation of the bacterium Clostridium botulinum type B (Bean strain), is a neuromuscular blocking agent (neurotoxin) and inhibitor of acetylcholine release at motor nerve terminals. 123 , 124 , 125 , 126

Mechanisms of action

Rimabotulinumtoxin B and other botulinum toxin serotypes act by inhibiting acetylcholine release at the neuromuscular junction via a three-step process, that is, toxin binding, toxin internalization, and inhibition of acetylcholine release into the neuromuscular junction leading to chemical denervation and flaccid paralysis. 123 , 124 , 126 , 127

Diseases treated

Rimabotulinumtoxin B is used for management of adults with cervical dystonia (also called as spasmodic torticollis) to reduce severity of abnormal head positioning and neck pain through reduction of undesired or excessive contraction of striated or smooth (involuntary) muscle. 128 , 129 , 130 , 131

Adverse reactions

The most common adverse effects reported with Botulinum toxin are dry mouth, dysphagia, dyspepsia, and injection site pain. 123 , 132 , 133 , 134 Serious hypersensitivity reactions have been rarely reported with onabotulinumtoxin A. 127

Botulism immune globulin/BabyBIG

Summary

Botulism immune globulin IV (BIG-IV) is a specific immune globulin (hyperimmune globulin) that is prepared from plasma of adult volunteer donors immunized with pentavalent botulinum toxoid, which neutralizes free botulinum toxin types A and B. It is one of the most poisonous substances known and exists in seven antigenic variants (types A to G). 120 , 121 , 135

Mechanisms of action

BIG-IV is a human-derived antitoxin that neutralizes botulinum toxin. BIG-IV has a half-life of approximately 28 days in vivo and large capacity to neutralize the toxin. 135

Disease treated

Infant botulism occurs when young infants ingest spores of Clostridium botulinum that then germinate, colonize the GI tract, and produce botulinum toxin. This neurotoxin causes generalized weakness and loss of muscle tone. A single infusion will neutralize the toxin for at least 6 months and toxins type A or B that may be absorbed from the colon of an infant younger than 1 year old. 121 , 135 , 136 , 137 , 138 , 139

Adverse effect

Mild, transient, blush-like erythematous rash on the face or trunk occurred in 9%–14% of infants receiving BIG-IV in clinical studies. 135 , 140

Rabies immune globulin/bayrab/HyperRAB, imogam Rabies, KedRAB

Description

Rabies immune globulin (RIG) is a sterile solution of specific IgG that contains antibody to rabies antigen. It is used to provide temporary passive immunity to rabies infection as part of a postexposure prophylaxis regimen in unvaccinated individuals exposed to the disease or virus. 141 , 142 , 143 , 144

Mechanisms of action

RIG is a human-derived antitoxin that neutralizes rabies virus so that virus spread is reduced and its infective or pathogenic properties are inhibited. Specific rabies antibodies present in RIG neutralizes rabies. It should be used in conjunction with rabies vaccine and can be administered through the seventh day after the first dose of vaccine is given. RIG provides immediate, temporary rabies virus-neutralizing antibodies until the patient responds to active immunization and produces virus-neutralizing antibodies. 121 , 141 , 142 , 143 , 144

Diseases treated

Given to all persons suspected of exposure to rabies with one exception, those who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine.

Adverse reactions

Most common local adverse effects include tenderness, pain, muscle soreness, or stiffness that may occur at the site of injection. Low-grade fever, headache, and malaise may also occur. 141 , 142 , 143

Immune Globulins: Immunomodulation

Rho(D) immune globulin/WinRho; RhoGam; Rhophylac, MicRhoGAM, BatRhoD, HyperRho

Summary

Rho(D) immune globulin (RhIG) consists of anti-Rho(D) IgG antibodies to the red blood cell Rho(D) antigen. RhIG is prepared from human pools of plasma of Rho(D)-negative donors immunized with Rho(D)-positive red blood cells after cold alcohol fractionation, and subsequent purification and infectious disease reduction technologies. 145 , 146 , 147 , 148 , 149 , 150

Mechanisms of action

The exact mechanism of action of Rho(D) immune globulin in the suppression of formation of anti-Rho(D) is not fully known.

In the treatment of preventing D alloimmunization, RhIG binds to Rho(D) antigen that entered the maternal circulation during fetal–maternal hemorrhage (FMH) involving an Rho(D)-positive fetus or transfusion with Rho(D)-positive blood, preventing stimulation of the mother's primary immune response to Rho(D) antigen. Therefore, by preventing the active production of anti-Rho (D) by the mother, the risk of hemolytic disease of the fetus and newborn in future pregnancies is decreased. 145 , 146 , 147 , 148 , 149

In the treatment of idiopathic thrombocytopenic purpura (ITP), administration of Rho(D) immune globulin to Rho(D)-positive individuals is believed to cause transient mononuclear macrophage Fc receptor (FcR) blockade by complexes within the reticuloendothelial system, particularly the spleen, which spares the patient's IgG-coated platelets. This FcR blockade and decreased Fc-mediated phagocytosis of antibody-coated platelets result in increases of platelet counts in ITP patients. 145 , 149 , 151 , 152 , 153 , 154 , 155 , 156

Diseases treated

Prevent D alloimmunization in D-negative women of childbearing potential if the neonate is D + , weak-D positive, or D untested, and following perinatal events associated with FMH such as abortion, ectopic pregnancy, amniocentesis, chorionic villus sampling, external cephalic version, abdominal trauma, and antepartum hemorrhage. It is also used to prevent D alloimmunization in D-negative individuals who receive D + blood components such as whole blood-derived platelets, apheresis platelets, and/or granulocytes. Similarly, it is used for the treatment of ITP in D + patients who had not undergone splenectomy. 145 , 146 , 147 , 149 , 151 , 152 , 153 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 Some preparations of Rho(D) immune globulin may be administered IM or IV (Rhophylac, WinRho SDF), whereas others are labeled for IM use only (MICRhoGAM, RhoGAM, HyperRHO S/D Full Dose, HyperRHO S/D Mini-Dose). 145 , 146 , 147 , 149 , 165 When used for ITP treatment, RhIG must be administered IV. 145 , 149

Adverse reactions

Generally, mild with the most common being headache, fever, chills, pain at the injection site and, rarely, hypersensitivity reactions. Some degree of hemolysis is inevitable, but this is predictable and transient. 146 , 147

Immunoglobulin (generic)/bbrands: Bivigam, Carimune, Cuvitru, Flebogamma, Gammagard, GamaSTAN, Gammaked, Gammaplex, Gamunex-C, Hizentra, Hyqvia, Octagam Privigen

Summary

Immune globulin IM (IMIG), immune globulin IV (IVIG), and immune globulin subcutaneous are sterile, nonpyrogenic preparations of globulins containing many antibodies normally present in adult human blood. Immune globulins (IG) are collected either by whole blood donations as recovered plasma (20%), or by apheresis as source plasma (80%). IVIG is a highly purified product consisting mostly of IgG with a half-life of 21–28 days.

Hyperimmune globulin (Hyper-Ig) products are manufactured from donors with high Ig titers with specificity to antigenic determinant(s) of interest. High titers of these donors can be achieved by natural immunity, prophylactic immunizations, or through targeted immunizations. Hyper-Ig products should contain at least fivefold-increased titers compared to standard preparations of IVIG.

IVIG production is regulated by the IUIS/WHO (International Union of Immunological Societies/World Health Organization), which require the following: • Source material must be plasma obtained from a minimum pool of 10,000 donors; • Product must be free of prekallikrein activator, kinins, plasmin, preservatives, or other potentially harmful contaminants; • IgA content and IgG aggregate levels need to be as low as possible; • Product must contain at least 90% intact IgG; • IgG should maintain opsonin activity, complement binding, and other biological activities; • IgG subclasses should be present in similar proportions to those in normal pooled plasma; • Antibody levels against at least two species of bacteria (or toxins) and two viruses should be determined; • Product must demonstrate at least 0.1 international units of hepatitis B antibody per mL, and hepatitis A radioimmunoassay titer of at least 1:1000; • Manufacturer should specify the contents of the final product, including the diluent and other additives, and any chemical modification of IgG. 166 , 167 , 168 , 169 , 170 , 171 , 172

Mechanisms of action

The mechanisms of Ig-induced immunomodulation are incompletely understood but include macrophage Fc receptor blockage by immune complexes formed between IVIG and native antibodies, modulation of complement, suppression of antibody production, suppression of inflammatory cytokines and chemokines, and/or antiidiotypic regulation of autoreactive B-lymphocytes or antibodies.

As IVIG contains a diverse group of antibody specificities, which protects recipients against multiple infections by eliminating opsonized infectious organisms via antibody-dependent cell-mediated cytotoxicity or by complement activation. This is followed by lysis and/or neutralization of soluble infectious proteins by immune complex formation and elimination through the RES. 166 , 170 , 173 , 174 , 175

Diseases treated

IVIG is indicated for the treatment of primary immune deficiency, secondary immune deficiency, ITP, Kawasaki disease, and congenital hypogammaglobulinemia. Currently, there is an extensive list of diseases for which IVIG could be used. It also has immunomodulatory properties resulting in an increasing list of both FDA-approved and nonapproved indications.

IMIG is used to provide passive immunity to hepatitis A virus infection for preexposure or postexposure prophylaxis in susceptible individuals who are at risk of or have been exposed to the virus. IMIG and IVIG are used to prevent or modify symptoms of measles (rubeola) in susceptible individuals exposed to the disease <6 days. IVIG is used for replacement therapy to promote passive immunity in patients with primary humoral immunodeficiency who are unable to produce sufficient amounts of IgG antibodies and in the management of ITP to increase platelet counts, to prevent and/or control bleeding, or to allow these patients to undergo surgery.

IVIG is used for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell Chronic Lymphocytic Leukemia. IVIG is used in conjunction with aspirin therapy for initial treatment of the acute phase of Kawasaki disease. IVIG is also used to treat chronic inflammatory demyelinating polyneuropathy to improve neuromuscular disability and impairment, and for maintenance therapy to prevent relapse. Furthermore, IVIG is used for maintenance treatment to improve muscle strength and disability in adults with multifocal motor neuropathy. 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201

Adverse reactions

Approximately 2%–10% of infusions are associated with adverse reactions that include those at the infusion site (erythema, pain, swelling, pruritus, heat), phlebitis, eczema, fever, chills, myalgias, malaise, flushing, rash, diaphoresis, pruritus, bronchospasm, chest pain, back pain, extremity pain, dizziness, blood pressure changes, nausea, vomiting, and headache. 167 , 170 , 172 , 177 , 178 , 179 , 181 , 182 , 183

Passive Monoclonal Antibody Treatment

In the late 20th century (∼1986), monoclonal antibodies were developed. The first monoclonal antibodies (Mabs) were of xenographic source and were wrought with problems of immunogenicity. These early Mabs did not gain favor until chimerization took pace in the mid-1990s, and in 1998 two Mabs were approved to treat one respiratory syncytial virus and the other certain breast cancers. Further development to humanize and then generate fully human Mab led to an evolution of therapies utilizing these agents. Mabs are being researched or approved to treat a multitude of diseases that include oncologic, inflammatory, autoimmune, cardiovascular, respiratory, neurologic, allergic, benign hematologic, infectious, orthopedic, coagulopathic, and metabolic indications and to decrease disease morbidity (diminution of pain), modify disease progression (i.e., macular degeneration, diabetes), and potentially alter anatomic development. In this section of the chapter, we will review the history of use of these passive monospecific antibody therapies, their mechanism of action, pharmacologic-therapeutic classification, particular medical indication, adverse reactions, and potential future use of these medications. 201

Mechanism of action

Depending on the antigenic target of these antibodies multiple events are set into action. Immunologic changes occur as the specific antigens are presented more efficiently to effector cells. Some of these actions create decreased inflammatory and allergic responses, while other effects generate antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Other actions can block receptor interaction with ligands by either binding with ligands or their cognate receptors (i.e., allow activation of NK cells). Interactions may also directly cause initiation of programmed cell death (apoptosis), cessation of growth/replication/proliferation, or lead to changes in metabolism. Moreover, there are also antibodies against infectious agents to prevent cell adhesion for entry, spread, replication, and contagion. Antibodies may also be directed against toxins leading to various methods of inactivation. 201

Adverse reactions

Depending on their mode of action, Mabs are associated with a myriad of side effects. They can be associated with immunogenicity that can cause a decrease in their effectiveness. Antineoplastic antibodies can be associated with tumor lysis syndrome. Similarly, reactivation of underlying infections can occur leading to progressive multifocal leukoencephalopathy, HBV, fungal, parasitic, or tuberculosis infections. Other adverse reactions include but are not limited to initiation of autoimmune disorders, increased risk for malignancy, cardiac arrhythmia, angina/ischemia, cytopenias, hemorrhage, and allergic reactions including anaphylaxis, embryo–fetal toxicity (if can cross placental barrier), and even death.

Types of Illness Treated

Oncology

Malignancies can be caused by infectious agents, toxins, or genetic mutations with changes in control of growth, proliferation, or programmed cell death. Historically these have been treated with a variety of radiation therapies to eradicate malignant cells or with chemotherapeutic agents to enhance maturity, decrease proliferation, or cause destruction of cancer cells. In some cases intense high-dose chemotherapy is used to cause cancer remission with stem cell transplants for subsequent rescue. Passive antibody therapy may replace or be additive to other pharmacology therapies and increase chances for complete remission, prolong disease-free survival, and overall survival.

B-cell chronic lymphocytic leukemia

Rituximab (Rituxan) is a chimeric murine/human Mab (IgG1κ) that binds to CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35 {controlling differentiation and possible calcium ion channel}). Its mechanism of action is not entirely clear and may involve CDC and ADCC. Many studies have shown this antibody to have an additive benefit to standard chemotherapy alone. This antibody has been approved by the FDA to treat chronic lymphocytic leukemia (CLL) since 1997. Nowadays, this medication is often combined with ibritumomab in treating CLL (to be discussed with non-Hodgkin's lymphoma). 202 , 203

Alemtuzumab (Campath) binds to CD52 and is a humanized rat Mab (IgG1κ) binding to receptors on both T and B cells as well as macrophages, NK cells, and neutrophils, leading to CDC and ADCC. The resultant cytopenias lead to a severe immunocompromised state. Alemtuzumab was FDA approved as a single agent in the treatment of B-cell CLL in 2001. 204

Ofatumumab (Ocrevus) is a human Mab (IgG1κ) with CDC that binds to CD20 near the cellular membrane. In phase II studies, this agent had 86% objective response rate (ORR) when used alone and with CHOP therapy had 100% ORR and 62% complete remission (CR); whereas, in phase III trials, this Mab showed ORR of 10% after rituximab relapse. This medication was approved by the FDA to treat CLL in 2009. 205

Monalizumab is a humanized Mab (IgG4κ) that binds to CD94/NKG2A (an inhibitory signal receptor transmitter) on NK cells. Monalizumab demonstrated blockade of NKG2A/HLA-E and restores the ability of NK cells to lyse B cells in vitro. In addition, this Mab was shown to be of benefit in murine models. Ongoing phase I/II studies will be completed in 2019. 206

Otlertuzumab is a humanized Mab fragment (IgG Fab’) with specificity to CD37 that induces both ADCC and caspase-independent apoptosis. In a phase II study both better progression-free survival (PFS) and ORR were observed when used with bendamustine compared to bendamustine used alone. 207

Urelumab is a human Mab (IgG4κ) with specificity to CD134 (an immune checkpoint inhibitor). This antibody has completed safety phase I dosing trials. Higher doses lead to significant hepatotoxicity. Safe dosing is now established in clinical phase II studies to be completed in 2020. 208 , 209

Ulocuplumab is a human Mab with specificity to CD184 (CXCR4). In vitro studies showed apoptotic effects via production of oxygen species that was not associated with better caspase activation than AMD3100. Phase I studies were completed in 2014, no manuscripts were found for review. This medication is presently in phase II trials against acute myelocytic leukemia (AML) to be completed in 2021. 210 , 211

Other monoclonal antibodies not demonstrating benefit in clinical trials for CLL include apolizumab, dacetuzumab, and gomiliximab (aka lumiliximab) 212 , 213 , 214 , 215

Acute myelocytic leukemia

AML is the leading cause of leukemic mortality in the United States (US). Over the last 10 years therapy has not changed significantly for this disease. Novel therapies have been developed in the last decade, some showing temporal success and some showing a brighter tomorrow. 216

AMG330 is a bispecific T-cell engager (BiTE) antibody with specificity for CD3 and CD33. This Mab is currently in clinical trials to be completed in 2020 for treatment of AML. A BiTE antibody stimulates ADCC (via T cells) in the presence of antigenic targets on cells of interest. In vitro studies have shown effective lysis of AML cells, while in animal studies it has demonstrated significant decrease in tumor burden. 217

IMGN632 is an anti-CD123 antibody complexed to a DNA mono-alkylating agent. In vitro studies showed it had more potency against AML cells than to normal myeloid progenitor cells. In animal models there was an excellent response rate against tumor cells. Ongoing clinical trials will be completed in 2021. 216

Talacotuzumab is a humanized monoclonal antibody (IgG1-2κ) with specificity to interleukin (IL)-3 receptor subunit-α (CD123, a growth and differentiating receptor). This antibody induces ADCC both in vitro and in animal models. Phase III clinical trials were reportedly completed in 2018; published results are forthcoming. 218

Samalizumab is a humanized Mab (IgG2/IgG4κ) with specificity to CD200 (OX-2membrane glycoprotein) is in phase II trials to be completed in 2021. 219

Ficlatuzumab is a humanized Mab (IgG1κ) in a phase I trial to treat refractory/relapsing AML to be completed in 2020. 220

Other Mab not demonstrating benefit in clinical trials or withdrawn following postmarketing for AML include gemtuzumab ozogamicin (FDA approved 2000 withdrawn 2010 secondary to venoocclusive disease) and lintuzumab ( no added benefit over standard chemotherapy). 221 , 222 , 223

Multiple Myeloma

Daratumumab (Darzalex) is a human Mab (IgG1κ) with specificity to CD38 (functions reportedly include receptor-mediated adhesion and signaling events, as well as important bifunctional ectoenzymatic activities that contribute to intracellular calcium mobilization. This Mab mechanism of action is thought to induce CDC, ADCC, antibody-dependent cellular phagocytosis, and apoptosis. This medication is used to treat refractory and recurrent multiple myeloma. 224 , 225

Silutuximab (Sylvant) is a chimeric Mab (IgG1κ) with specificity to IL-6. This medication was FDA approved in 2014 for multicentric Castleman's disease (MCD) with HIV negative and HHV-8 negative. There are ongoing studies in phase II clinical trials to be completed in 2019. 226 , 227

B-cell acute lymphoblastic leukemia (B-cell ALL)

Blinatumomab (Blincyto) is a mouse double heavy-chain fragment (Murine {scFv - kappa – heavy} – {scFv - heavy – kappa}) with specificity for CD19 and CD3 known as a BiTE. This Mab's mode of action is by directing CD3 + effector memory T cells to CD19 + target cells leading to T-cell activation and B-cell apoptosis. This biologic is used to treat relapsed/refractory cell ALL. In phase III trials event-free survival almost tripled and duration of remission almost doubled. 228 , 229 , 230

Hodgkin's lymphoma

Hodgkin's lymphoma is a rare malignancy affecting young adults with a peak incidence in patients >55 years old. Up to 40% of these patients can develop relapsing disease. Brentuximab vedotin (Adcentrix) is a chimeric humanized Mab drug conjugate (Mab + linker + payload {IgG1κ +protease cleavage linker + monomethyl auristatin E [MMAE]}) with specificity to CD30 (a cell membrane protein of the tumor necrosis factor receptor superfamily member 8. MMAE is a microtubule-disrupting agent. The combination of this a Mab and drug conjugate disrupts the intracellular microtubule network causing cell cycle arrest at G2/M stage and apoptosis. This medication has a 43% PFS at 30 months. 231

Mab to look out for in the future include Camidanlumab tesirine (ADCT-301) a human Mab (IgG1κ). This Mab has specificity to CD25 (a IL-2 receptor alpha subunit) with a drug conjugate. The drug is released intracellularly and causes DNA interstrand crosslinks. This Mab is in phase I studies to be completed in 2019 for Hodgkin's and non-Hodgkin's T- and B-cell lymphomas. In addition, there are clinical phase I studies against multiple solid tumors to be completed in 2021. 232 , 233

Agents abandoned or not found to be beneficial include apolizumab, denintuzumab mafodotin (HBU-12), iratumumab (MDX060), and lucatumumab (HCD122). 212 , 234 , 235

Anaplastic large cell lymphoma

Brentuximab vedotin (Adcentrix) is an FDA-approved medication for patients with refractory or relapsed anaplastic large cell lymphoma who achieved CR. This Mab had 79% OS and 57% PFS at 5 years, with median response duration not reached at time of publication. 236

Breast Cancer

Atezolizumab (Tecentriq) is an FcγR binding–deficient, fully humanized Mab (IgG1κ). This Mab binds to programmed death ligand I (PD-L1) to prevent interaction with receptors PD-1 and B7.1 (a costimulatory cell-surface protein), reversing T-cell suppression. Activation of B7.1 can potentially stimulate long-term responses through development of new immunity via priming and activation of T cells in lymph nodes. A lack of FcγR binding decreases ADCC of the T cells enabling more tumor-specific T cell to remain active. This medication was approved by the FDA in 2019 to treat triple negative (estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2) unresectable or metastatic breast cancers. 237 , 238

Colorectal Cancer

Bevacizumab (Avastin) is a humanized Mab (IgG1κ) with specificity to vascular endothelial growth factor-a (VEGF-A) that acts as an inhibitor of angiogenesis. It was FDA approved for treatment of colorectal cancer and has recently been approved for multiple other cancers including ovarian, fallopian cancers, renal cell carcinoma, and recurrent glioblastoma multiforme (GBM). 239 , 240

Urothelial Carcinoma

Atezolizumab (Tecentriq) is FDA approved as a single agent in urothelial carcinoma and for patients with disease progression despite other chemotherapy treatment. 241 , 242

Nonsmall cell lung cancer

Atezolizumab (Tecentriq) is FDA approved as a single agent for nonsmall cell lung cancer (NSCLC).

Bevacizumab (Avastin) is FDA approved for treatment of locally advanced, recurrent or metastatic, nonsquamous NSCLC.

Nivolumab (Opdivo) is an FDA-approved human Mab (IgG4κ) immunoglobulin and blocks PD-1 preventing interaction PD-1 and its ligands PD-L1 and PD-L2. It is used to treat RCC, NSCLC, Hodgkin's lymphoma, melanoma, small cell lung cancer, colorectal cancer, and squamous cell carcinoma of the head and neck. In phase III clinical trials, nivolumab performed better than docetaxel in the treatment of NSCLC. 243 , 244 , 245

Ovarian/cervical fallopian cancer

Bevacizumab (Avastin) is FDA approved for treatment of locally advanced, recurrent or metastatic, ovarian, cervical, and fallopian cancers after treatment with chemotherapy regimens and surgery. 246

Merkel Cell Carcinoma

Merkel cell carcinoma is a rare aggressive cutaneous malignancy caused by infection with polyoma virus and exposure to ultraviolet radiation. This cancer was classically treated with chemotherapeutic agents leading to rare durable responses. Avelumab (Bavencio) is a fully human Mab (IgG1λ) with specificity to PD-L1. This Mab was approved by the FDA for treatment of Merkel cell carcinoma in 2017. Treatment with this Mab increases response rates to about 50% and extended durable response times approximately five times. 247 , 248 This Mab is in clinical trial to treat other solid tumors including but not limited to hepatocellular, ovarian, esophagogastric, colorectal NSCLC, testicular, urothelial, and adrenocortical carcinomas. 249

Neuroblastoma

Neuroblastoma is an aggressive tumor of children with a 5-year survival of about 50%. Treatment classically is high-dose intensive chemotherapy, myeloablative chemotherapy with stem cell rescue, and/or irradiation therapy. Dinutuximab (Unituxin) is a chimeric Mab (IgG1κ) with specificity to GD2 ganglioside that has mechanisms of action via CDC and ADCC. This Mab is used in patients who have had at least a partial response to classic therapy. 250 , 251

Glioblastoma Multiforme

GBM is the most common malignant primary brain tumor in adults. This disease remains incurable.

Bevacizumab (Avastin) is FDA approved for treatment of recurrent GBM as salvage therapy. This medication with chemotherapy increases overall survival by 4 months but as a single agent is not effective. 252

Relatlimab (BMS-986,016) is a human Mab (IgG4κ) with specificity to lymphocyte activation gene 3 (LAG3, CD223) and is in phase I clinical trials to be completed in 2020 for treatment of GBM. 253

Tanibirumab (aka Olinvacimab, TTAC-0001) is a human Mab (IgG1) with specificity to vascular endothelial growth factor receptor-2 (VEFR-2) and is in phase II studies to treat GBM to be completed in 2020. 254 , 255 , 256

Malignant Ascites

Catumaxomab (Removab) is a trifunctional rat/murine hybrid antibody (IgG2a/IgG2b). Catumaxomab consists of one “half” (one heavy chain and one light chain) of an antiepithelial cell adhesion molecule (anti-EpCAM) antibody and one-half of an anti-CD3 antibody, so that each molecule of catumaxomab can bind both EpCAM and CD3. In addition, the Fc-region can bind to an Fc receptor on accessory cells such as other antibodies, which has led to calling the drug a trifunctional antibody. This antibody's mechanism of action is through ADCC. It is approved for use in Europe for malignant ascites from ovarian, gastric, colon, pancreatic, breast, and endometrial carcinoma and is a pending review for approval by the FDA. 257 , 258 , 259 , 260

Cutaneous squamous cell carcinoma

Cemiplimab (Libtayo) is a human Mab (IgG4) for treatment of cutaneous squamous cell carcinoma (CSCC) that is metastatic or locally advanced and not amenable to surgery. CSCC is second only to basal cell carcinoma as the most common skin cancer. Surgical intervention is not possible in 5% of patients. This Mab offers a treatment with less morbidity than palliative radiation or surgery, and gives an ORR in 50% of these otherwise untreatable patients. There are many additional phase II studies involving this Mab to be completed from 2020 to 23. 261 , 262

Autoimmune/Inflammatory Diseases

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) pathophysiology remains unknown but may have genetic, infectious, autoimmune origins including cell-mediated immunity. These diseases may be classified as ulcerative colitis (UC), isolated to the colon, or Crohn's disease primarily found in the colon but may involve the entire gastrointestinal tract. With long-standing active disease, malignancy is much more frequent in UC than in Crohn's disease. Mild UC is treated with antiinflammatory agents such as sulfasalazine and glucocorticosteroids. For more severe disease, high-dose steroids may be used to maintain disease quiescent and low-dose steroids to keep disease in remission. Low-dose chemotherapeutic agent or immunosuppressive agent may also be added if dose of corticosteroids is too high to maintain remission. Surgery may be necessary to control disease. For Crohn's disease, medical therapy is usually less successful in managing the disease and surgery may be necessary but is not curative as in UC. For both of these disease processes, passive antibody therapy may offer not only control of disease but possible complete remission from mucosal damage. 263 , 264

Adalimumab (two formulations: Humira and Amjevita) is a recombinant human Mab (IgG1) with specificity to tumor necrosis factor alpha (TNF-α). Both forms are FDA approved to treat Crohn's disease as well as multiple types of rheumatoid arthritis. In Crohn's disease, this medication decreases signs and symptoms of disease and is able to induce clinical remissions. 265 , 266

Certolizumab (Cimzia) is a recombinant humanized m fragment with TNF-α as target. It is FDA approved for both Crohn's disease and Rheumatoid arthritis. 267 , 268 , 269

Vedolizumab (Entyvio) is a humanized Mab (IgG1κ) that has selectivity for integrin α4β7 and is FDA approved for treatment of Crohn's disease. This Mab mode of action is to selectively block trafficking of memory T cells into inflamed gut tissue by inhibiting α4β7-mucosal addressin cell adhesion molecule-1 (MAd-CAM-1) interaction with intestinal vasculature. This medication has shown a good safety profile with no cases of promyelocytic leukemia (PML), no increased risk of infections, malignancies compared with classically treated IBD, and low incidence of infusion-related reactions. This medication is also FDA approved for UC. 270 , 271

Infliximab (Remicade, Inflectra, Remsira) is a chimeric Mab (IgG1κ) with specificity to TNF-α and is FDA approved for IBD and multiple inflammatory arthritic diseases. This medication allows for steroid-free remission within months of starting therapy. 272

Natalizumab (Tysabri) is a humanized Mab (IgG2κ) with selectivity to CD62L (L selectin α4 subunit of α4β1 and α4β7 integrins of leukocytes, not neutrophils, VLA-4). This Mab is FDA approved for Crohn's disease and multiple sclerosis. This medications is effective in induction of clinical remission in moderate-to-severe Crohn's disease. This medication does have the risk of PML. 273 , 274

Other Mab being studied for Crohn's disease but not yet approved by the FDA include Ustekinumab, brazikumab, etrolizumab, risankizumab, and ontamalimab. In contrast, Mabs studied but not beneficial for Crohn's disease include andecaliximab, eldelumab, and fontolizumab. Refer to Table 16.1 . Table 16.1 Summary of Monoclonal Antibody Therapies. Generic Drug Name Brand Name Type of Antibody AHFS Classification Dosage Form(s) Target 8H9 Iodine 124 monoclonal antibody (Murine) Antineoplastic Neuroblastoma, sarcoma, metastatic brain cancers Another study Sloan Kettering using I 331 version phase I good results Intravenous B7–H3 Abagovomab Monoclonal antibody (Murine) An antiidiotypic mAb that mimics ovarian cancer CA125 protein Antineoplastic Phase II study for ovarian cancer Phase III good immune response but no increase RFS or OS no benefit Subcutaneous CA-125 Abatacept Orencia FDA 2005 EU 2010 Recombinant soluble fusion protein of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1). Disease modifying Rheumatoid arthritis Juvenile and adult psoriatic arthritis (phase III) Subcutaneous or intravenous Selective costimulation modulator, inhibits T cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Abciximab c7Ec Fab ReoPro FDA 1994 EU 1995 (country-specific approval) Human-murine chimera Recombinant monoclonal IgG1 Fab Procedure modification High-risk coronary intervention Platelet aggregation inhibitor Intravenous Platelet glycoprotein IIb/IIIa receptor (CD41 7E3)/Intergrin α-IIb Abituzumab DI17E6 EMD525797 Humanized monoclonal antibody IgG2κ Antineoplastic Colorectal cancer phase I 2013, phase II 2015 primary endpoint PFS not met Sclerosing interstitial lung disease phase II terminated 2018 slow enrollment Prostate phase IIno significant increase PFS Intravenous CD51 (?integrin alpha V) Abrilumab AMG 181 Phase II study discontinued development (2016) Integrin α-4 β-7 Actoxumab Human monoclonal antibody Disease modifying Clostridium difficile Phase I and II anti-CDTB1 much better Clostridium difficile toxin A Adalimumab Humira FDA 2002 EU 2003 Amjevita FDA 2016 EU 2017 Recombinant human IgG1 monoclonal antibody Disease modifying Humira Rheumatoid arthritis; juvenile idiopathic arthritis; psoriatic arthritis; ankylosing spondylitis; Crohn's disease, plaque psoriasis Amjevita Arthritis; juvenile rheumatoid arthritis; psoriatic arthritis; rheumatoid colitis; ulcerative Crohn's disease; psoriasis; spondylitis; ankylosing Possibly hemolytic disease of newborn Injection subcutaneous TNF-α Adecatumumab MT-201 Recombinant human monoclonal antibody IgG1κ Antineoplastic Breast phase Ib+, colorectal and prostate Phase II completed Phase III soon? Intravenous EpCAM (CD326) epithelial cell adhesion molecule Aducanumab Human monoclonal antibody IgG1 Disease modifying Alzheimer's disease Phase III x 2 ongoing started 2015 Intravenous Beta-amyloid (N-terminus 3–6) soluble oligomers and insoluble fibrils Afasevikumab Human monoclonal antibody IgG1κ Disease modifying Multiple sclerosis Phase I completed Nothing in pubmed Subcutaneous IL17A and IL17F Afelimomab Murine F(ab') Antibody Fab’ fragment IgG3κ Disease modifying Sepsis Phase III trial marginal benefit abandoned TNF-α Alacizumab pegol Humanized monoclonal antibody F(ab') 2 Limited information on development; Cancer VEGFR2 Alemtuzumab LDP-03 Campath-1H Lemtrada FDA 2014 EU 2013 MS Campath FDA 2001 EU 2001 CLL Humanized rat monoclonal antibody IgG1κ Antineoplastic B-Cell CLL , CTCL, T cell lymphoma Disease modifying Multiple sclerosis (phase III) Not effective for kidney transplant conditioning or rejection prevention Intravenous CD52 Alirocumab Praluent FDA 2015 EU 2015 Human monoclonal antibody IgG1 Disease modifying Decrease cholesterol Phase III Subcutaneous Proprotein convertase subtilisin kexin type 9 (PCSK9) Altumomab pentetate In 98 Hybri-ceaker Murine monoclonal antibody IgG1 Diagnostic purpose radiology colorectal cancer (diagnosis) CEA ALX-0171 Trimeric nanobody Antiinfectious RSV phase II 2020 Inhalation RSVF Amatuximab MORAb-009 Chimeric murine-human monoclonal antibody IgG1κ Antineoplastic Ovarian cancer Phase II Now research on using to treat mesotheliomas Phase I/II Pancreatic cancer Intravenous Mesothelin Prohibits binding of MSLN with antigen CA125/MUC16 AMG330 Bispecific T-cell engager (BiTE) Antineoplastic AML phase I AML 2020 Intravenous CD33 and CD3 Anatumomab mafenatox Murine monoclonal fragment Fab Antineoplastic Nonsmall cell lung carcinoma Tumor-associated glycoprotein 72 (TAG-72) Andecaliximab GS 5745 Chimeric monoclonal antibody IgG4κ Antineoplastic gastric cancer phase I, II, III ongoing or gastroesophageal junction adenocarcinoma phase III ongoing Crohn phase II no response, UC Intravenous Gelatinase B is a matrix metalloproteinase-9 (MMP-9) Anetumab ravtansine In 98 Human monoclonal antibody IgG1λ Antineoplastic ovarian phase II, lung, pancreatic phase I, breast now research on using to treat mesotheliomas Phase II Cervical cancer ?preclinical Mesothelin Prohibits binding of MSLN with antigen CA125/MUC16 Anifrolumab Human monoclonal antibody IgG1κ Disease modifying Systemic lupus erythematosus phase I and IIb 2018 Intravenous Interferon α/β receptor Anrukinzumab (=IMA-638) Humanized monoclonal antibody IgG1κ Disease modifying Asthma phase II ?results UC phase II no benefit IL-13 Apolizumab Humanized monoclonal antibody Antineoplastic non-Hodgkin's lymphoma abandoned 2009 toxic effects 2009 CLL phase I/II HLA-DRβ Arcitumomab CEA-Scan FDA 1996 EU 1996 Withdrawn EU market 2005 Murine monoclonal antibody IgG1 Fab' Diagnostic imaging Gastrointestinal cancers Colorectal cancers CEA Ascrinvacumab Human monoclonal antibody Antineoplastic mesothelioma Nothing in pub med or web search Activin receptor-like kinase 1 Aselizumab Humanized monoclonal antibody Disease modifying Severe injured patients phase II 2004, no benefit L-selectin (CD62L) Atezolizumab MPDL3280A Tecentriq FDA 2016 Fc engineered, humanized monoclonal antibody IgG1κ Antineoplastic agent, treat metastatic urothelial carcinoma , non-small cell lung cancer Phase III Bladder/urothelial cancer phase I Breast cancer phase Ib triple marker neg breast cancer Intravenous Binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors FDA-approved atezolizumab (TECENTRIQ, Genentech, Inc.), in combination with bevacizumab, paclitaxel, and carboplatin for the first-line treatment of patients with metastatic nonsquamous, nonsmall cell lung cancer (NSq NSCLC) with no EGFR or ALK genomic tumor aberrations Atidortoxumab Human monoclonal antibody IgG1κ Limited information on use and development Negative search PubMed-internet Staph aureus alpha toxin Atinumab Human monoclonal antibody IgG4κ Disease modifying Acute spinal cord injury RTN4 Atorolimumab Developed?? Human monoclonal antibody IgG3 Disease modifying hemolytic disease of the newborn Rhesus factor Avelumab Bavencio FDA 2017 Human monoclonal antibody IgG1λ Antineoplastic Cancers, ovarian, gastric, nonsmall cell lung (NSCLC), metastatic, solid tumors phase II Studies completed metastatic Merkel cell carcinoma Intravenous PD-L1 Azintuxizumab vedotin Chimeric/humanized monoclonal antibody IgG1 Antineoplastic Nothing in PubMed CD319 BAN-2401 Humanized monoclonal antibody IgG1 Disease modifying Alzheimer A phase IIb study ongoing started 2013 Intravenous Soluble Aβ amyloid protofibrils Bapineuzumab Humanized IgG1 monoclonal antibody Disease modifying Alzheimer's disease Phase III no more studies discontinued research 2012 ARIA-E, amyloid-related imaging abnormalities–edema Intravenous Beta amyloid Fibrillary and soluble β amyloid Basiliximab Simulect FDA 1998 EU 1998 Chimeric monoclonal antibody IgG1κ Immunosuppressive agents Prophylaxis of acute rejection in allogeneic renal transplantation Intravenous CD25 (α chain of IL-2 receptor) Bavituximab Chimeric monoclonal antibody IgG1κ IgG3 (SUNRISE trial) Cancer, viral infections (Hep C) phase III NSCLC failed to improve survival Sunrise trial stopped Feb 2016, phase II/III breast cancer, phase II pancreatic cancer, phase I/II trial hepatocellular carcinoma, phase I malignant melanoma + rectal cancer good response rectal; not for prostate cancer, phase II hepatitis C not resulted? Phosphatidylserine BAY-103356 CDP 571 Humicade Senlizumab Humanized monoclonal antibody IgG4κ For research only Phase II 1995 TNF α BCD-100 Human monoclonal antibody Antineoplastic Phase II/III melanoma NCT03269565 (complete Dec 2019) Intravenous Programmed cell death-1 (PD1) Bectumomab LymphoScan Fab’-IgG2κ Antineoplastic Non-Hodgkin's lymphoma (detection) CD22 Begelomab Begedina Murine IgG2b Disease modifying GvHD phase II/III DPP4 binds CD26 on T lymphocytes Belantamab mafodotin Humanized monoclonal antibodymab Antineoplastic No studies or info on clinical trial, PubMed, FDA substance BCMA Belatacept Nulojix FDA 2011 Soluble fusion Protein consisting of the modified extracellular domain of CTLA-4 fused to Fc domain of a recombinant human monoclonal antibody IgG1 Immunosuppressive agents Prophylaxis renal transplant rejection in adults Phase III FDA approved Intravenous Selectively inhibits T-cell activation through costimulation blockade binds to both CD80 and CD86 blocking CD28 Belimumab Benlysta FDA 2011 EU 2011 LymphoStat-B Human monoclonal antibody IgG1λ Disease modifying Kidney transplant phase II Treat SLE (testing phase III for renal involvement) Phase II Rheum arthritis failure Phase II Srogren ± GVHD ongoing Intravenous Subcutaneous B-cell activating factor (BAFF), B-lymphocyte stimulator Bemarituzumab Humanized monoclonal antibody Antineoplastic FGFR2 Benralizumab Fasenra FDA 2017 EU 2017 Humanized monoclonal antibody IgG1κ Disease-Modifying Asthma phase III completed Severe asthma eosinophilic subtype Subcutaneous Interleukin-5 (IL-5α) receptor alpha subunit-directed cytolytic (CD125) Berlimatoxumab Human monoclonal antibody Staph aureus bicomponent leukocidin No studies clinical, no find creative, zero pub med Bermekimab MABp1 T2-18C3 CA-18C3 Xilonix Human monoclonal antibody IgG1κ Disease modifying psoriasis phase III x 2 2020 Ank spond II 2022 Psor arth II 2020 III 2020 Subcutaneous Intravenous IL17A Bersanlimab Human monoclonal antibody ICAM-1 Bertilimumab CAT-214 Human monoclonal antibody IgG4κ Disease modifying Severe allergic disorders phase II atopic dermititis Ongoing studies bullous pemphigoid and ulcerative colitis phase II Intravenous CCL11 (eotaxin-1) Besilesomab Scintimun EU 2010 Not FDA approved Murine monoclonal antibody IgG1κ Diagnostic use Inflammatory lesions and metastases (detection) CEA-CAM8-related antigen Bevacizumab Avastin FDA 2004 EU 2005 Humanized monoclonal antibody IgG1κ BiTE Antineoplastic agent Antiangiogenesis inhibitor Colorectal cancer 2004, NSCLC 2006, RCC 2009, GBM phase III, ovarian cancer, metastatic cervical cancer, fallopian 2014 Breast cancer (FDA removed approval for breast cancer 2010) Recurrent glioblastoma multiform Non squamous nonsmall cell lung cancer Intravenous solution or ophthalmic injection May not be so good for GBM or ovarian VEGF-A anti-angiogenesis inhibitor Bezlotoxumab Zinplava FDA 2016 EU 2017 Human monoclonal antibody IgG1 Disease modifying phase III studies done MODIFY I and II Modify III ongoing Pseudomembranous colitis Intravenous Clostridium difficile colitis anti-B toxin Biciromab FibriScint Murine monoclonal fragment Fab’ IgG1κ Detect cardiovascular thromboembolism (diagnosis) Fibrin II, beta chain Bimagrumab BYM338 Human monoclonal antibody IgG1λ Disease modifying Myostatin inhibitor DM II decrease BMI phase II Sporadic inclusion body myositis phase III not meet endpoint Treat sarcopenia in older adults phase II Intravenous Activin A receptor type IIB (ACVR2B) Bimekizumab Humanized monoclonal antibody IgG1κ Disease modifying Ankylosing spondylitis (2018 II, 2022 II, +), plaque psoriasis (2021 III, 2020 III, 2019 III, +), psoriatic arthritis (2020), RA (2017 II), UC phase II Subcutaneous IL 17A and IL 17F Bivatuzumab mertansine Humanized monoclonal antibody IgG1 Antineoplastic squamous cell carcinoma, breast phase I fail x 2, head/neck or esophagus phase I fail, toxicity CD44 v6 Bleselumab Human monoclonal antibody IgG4κ Disease modifying organ transplant rejection phase II 2020 to prevent FSGS in kidney transplant patients Phase II psoriasis- medication tolerated with minimal reaction, no benefit to disease process Intravenous CD40 Blinatumomab Blincyto FDA 2014 EU 2015 Murine(scFv - kappa - heavy) - (scFv - heavy - kappa) BiTE Antineoplastic Ph chrom neg pre-B ALL (CD19+) phase II B- cell precursor acute lymphoblastic leukemia (ALL) initial or relapsed/refractory Intravenous Bispecific T-cell engager monoclonal antibody construct that directs CD-3 positive effector memory T cells to CD19-positive target cells Blontuvetmab Blontress Canine monoclonal antibody IgG2 κ/λ Veterinary treat canine B-cell lymphoma CD20 Blosozumab Humanized IgG4κ Disease modifying Osteoporosis 3 phase I and one phase 2 injection site reaction and antibodies to antibody Intravenous Subcutaneous SOST Antisclerostin Bococizumab RN316 PF-04950615 Humanized IgG2κ Disease modifying Dyslipidemia Phase III 2019 Discontinued secondary to antidrug antibodies, no primary endpoint achieved Subcutaneous intravenous Neural apoptosis-regulated proteinase 1 PCSK9 (proprotein convertase subtilisin/kexin type 9, neural apoptosis-regulated convertase 1, NARC1, NARC-1, proproteine convertase 9, PC9) Brazikumab Human monoclonal antibody IgG2λ Disease modifying Ulcerative colitis phase II 2021 Phase I/II completed Crohn. Phase III ongoing Subcutaneous IL23 Brentuximab vedotin Adcetris FDA 2013 Breakthrough therapy status by FDA 2018 Chimeric humanized monoclonal antibody IgG1κ Antineoplastic Hodgkin lymphoma Anaplastic large-cell lymphoma Intravenous CD30 (TNFRSF8) an antibody-drug conjugate (ADC) 3 parts: anti-CD30 (cAC10, a cell membrane protein of the tumor necrosis factor receptor), a microtubule disrupting agent monomethyl auristatin E (MMAE) and a protease-cleavable linker that attaches MMAE covalently to cAC10. The combination disrupts the intracellular microtubule network causing cell-cycle arrest and apoptotic cellular death Briakinumab Human monoclonal antibody Disease modifying psoriasis, Drug development stopped for psoriasis, phase IIb study in Crohn's Intravenous IL-12, IL-23 Brodalumab AMG827 Siliz FDA 2016 Human monoclonal antibody IgG2κ Disease modifying Plaque psoriasis Completed phase III Subcutaneous Receptor IL-17RA Brolucizumab RTH258 ESBA1008 FDA review 2018 Humanized single chain antibody fragment (scFv κ) Disease modifying Wet or age-related macular degeneration phase III to be completed Sept 2018, 2020 HAWK ( NCT02307682 ) and HARRIER ( NCT02434328 ) phase III trials good results Intravitreal https://www.novartis.com/news/media-releases/new-novartis-phase-iii-data-brolucizumab-demonstrate-reliability-12-week-treatment-interval VEGFA Brontictuzumab Humanized IgG2λ Antineoplastic Phase I Colorectal Lymphoid Adenoid cystic Solid tumors Intravenous Notch 1 Burosumab KRN23 Crysvita FDA 2018 Human monoclonal antibody IgG1κ Disease modifying X-linked hypophosphatemia Phase III completed Subcutaneous https://www.creativebiolabs.net/burosumab-overview.htm FGF 23 phosphaturic hormone fibroblast growth factor 23 Cabiralizumab Humanized monoclonal antibody IgG4κ Antineoplastic metastatic pancreatic cancer phase II 2020 Many other cancers phase I Intravenous CSF1R Camidanlumab tesirine ADCT-21 Human monoclonal antibody Antineoplastic B-cell Hodgkin's lymphoma, non-Hodgkin lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia 2018 phase I Advanced solid tumors with literature evidence of CD25(+) treg content Head and neck Nonsmall cell lung Gastric, esophageal, Pancreas, bladder, Renal cell, melanoma, Triple-negative breast, ovarian phase I 2021 Intravenous CD25 Sinilimab Camrelizumab IBI308 China pending approval Humanized monoclonal antibody IgG4κ Antineoplastic Phase III nasopharyngeal cancer 2021 Phase III esophageal cancer 2021 Programmed cell death 1 (PDCD1) Canakinumab ACZ885 Ilaris FDA 2009 EU 2009 Human monoclonal antibody IgG1κ Disease modifying Cryopyrin- associated periodic syndromes Including familial cold auto-inflammatory syndrome and Muckle –Wells syndrome ; tumor necrosis factor receptor-associated periodic syndrome (TRAPS); hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) and familial Mediterranean fever (FMF) Systemic Juvenile idiopathic arthritis Treat Juvenile idiopathic arthritis phase III NSCLC 2025 phase III CVD rejected by FDA Behcet Subcutaneous IL-1β Cantuzumab mertansine Humanized monoclonal antibody IgG1κ Antineoplastic Colorectal cancer phase I 2007 Intravenous Mucin CanAg Cantuzumab ravtansine Humanized monoclonal antibody IgG1κ Antineoplastic Cancers MUC1 Caplacizumab-yhdp Cablivi (Nanobody program) FDA 2019 EU 2018 Humanized single variable domain antibody (bivalent nanobody) Disease modifying Inhibits interaction vWF and platelets Treat acquired TTP Phase III Hercules study completed Intravenous Subcutaneous VWF Capromab pendetide Prostascint FDA 1996 Murine monoclonal antibody Diagnostic imaging Prostatic carcinoma cells detection Intravenous Tumor surface antigen PSMA Carlumab Human monoclonal antibody IgG1κ Antineoplastic Prostate phase II no long term benefit Pulm fibrosis phase II no benefit Intravenous hMCAF/MCP-1 (human macrophage/monocyte chemotactic protein-1) Carotuximab TRC105 Chimeric monoclonal antibody IgG1κ Antineoplastic angiosarcoma Hepatocellular car phase I/II 2020 Glioblastoma multi-phase II 2014 terminated poor accrual ?results Angiosarcoma phase III 2019 TAPPAS trial Prostate ca phase II 2021 NSCLC phase I 2019 Intravenous Endoglin (CD105) Catumaxomab Removab FDA approved pend 2017) EU approved 2009 Removab: A trifunctional rat/murine hybrid antibody IgG2a/IgG2b Antineoplastic Removab Ovarian cancer phase II, malignant ascites phase II, gastric cancer phase II (ovarian, gastric, colon, pancreatic, breast, endometrial) Proxinium Head and neck cancer Intraperitoneal EpCAM, CD3 Catumaxomab consists of one “half” (one heavy chain and one light chain) of an anti-EpCAM antibody and one half of an anti-CD3 antibody, so that each molecule of catumaxomab can bind both EpCAM and CD3. In addition, the Fc-region can bind to an Fc receptor on accessory cells like other antibodies, which has led to calling the drug a trifunctional antibody. cBR96-doxorubicin immunoconjugate aka SGN-15 Humanized monoclonal antibody IgG1κ Antineoplastic Cancer Sponsorship ceased 2005 Cedelizumab CIMZIA Humanized monoclonal antibody IgG4κ Prevent organ transplant rejection CD4 Cemiplimab Libtayo FDA 2018 Human monoclonal antibody IgG4 Antineoplastic Nonsmall cell lung cancer (NSCLC) phase I 2021, phase III 2022 × 3 Oropharynx phase II 2022 Multiple myeloma phase II 2022 Ovarian ca phase II 2022 Head neck squamous cell carcinoma phase II 2020 Cutaneous squamous cell Glioblastoma multiforme phase II 2021 Lung ca phase II 2022 Cervical cancer phase III 2023 Intravenous Programmed cell death receptor PCDC1 Cergutuzumab amunaleukin Aka RO6895882, CEA-IL2v Humanized monoclonal antibody Antineoplastic phase I Dec 2018 Intravenous IL2 Certolizumab pegol CDP870 Cimzia FDA 2008 EU 2009 Recombinant, humanized antibody Fab’ fragment Disease-Modifying Crohns Rheumatoid arthritis (phase IIIs completed) Psoriatic arthritis phase III Ankylosing spondylitis Subcutaneous Tumor necrosis factor α blocker Cetrelimab Relatimab Human monoclonal antibody IgG4κ Antineoplastic Nothing on PubMed or creative lab Substance is registered with FDA Programmed cell death 1 Cetuximab IMC-225 Leukeran Erbitux FDA 2004 EU 2004 Recombinant chimeric monoclonal antibody IgG1κ Antineoplastic agent Metastatic colorectal cancer and head and neck cancer NSCLC Intravenous solution EGFR Citatuzumab bogatox Humanized Fab IgG1κ Antineoplastic ovarian cancer and other solid tumors Study phase I terminated 2008 EpCAM Cixutumumab Human monoclonal antibody IgG1κ Antineoplastic Solid tumors Sarcoma phase II Esophageal cancer phase II Rhabdomyosarcoma phase II no benefit Liver cancer phase I Low antitumor effect Pancreas no benefit 2012 Intravenous IGF-1 receptor (CD221) Clazakizumab ALD−518 Humanized monoclonal antibody Disease modifying rheumatoid arthritis phase II 2015 × 3 Crohn disease phase II 2013 Highly sensitized renal transplant candidates phase II 2020 Treat post-tx rejection kidney phase II 2020 Antibody-mediated rejection phase III 2027 Subcutaneous IL6 Clenoliximab Chimeric monoclonal antibody Disease modifying Rheum Arth No study since 2003 CD4 Clivatuzumab tetraxetan (90)Y-clivatuzumab tetraxetan hPAM4-Cide Humanized monoclonal antibody IgG1κ Antineoplastic Pancreatic cancer Phase III 2017 PANCRIT-1 study. Study terminated no increase improvement of overall survival MUC1 Codrituzumab Humanized monoclonal antibody IgG1κ Antineoplastic HCC Phase Ib no response Phase II no response Glypican 3 Cofetuzumab pelidotin Humanized monoclonal antibody IgG1κ Antineoplastic Nothing on PubMed or creative lab Substance is not registered with FDA Protein tyrosine kinase 7 (PTK7) Coltuximab ravtansine SAR3419 Chimeric monoclonal antibody IgG1 conjugated to DM4 (N2′-(4-((3-carboxypropyl)dithio)-4-methyl-1-oxopentyl)-N2′-deacetylmaytansine) Antineoplastic Relapse/refractory ALL phase II 2015 low clinical response Phase II moderate response CD19 Conatumumab AMG655 Human monoclonal antibody IgG1κ Antineoplastic Phase II 2019: Advanced solid tumors Carcinoid Colorectal cancer Locally advanced Lymphoma Metastatic cancer Nonsmall cell lung cancer Sarcoma Solid tumors Colon cancer phase Ib/II no benefit Intravenous TRAIL-R2 Concizumab Humanized IgG4κ Disease modifying Hemophilia A and B phase II 2020 Subcutaneous Kunitz-type protease inhibitor 2 domain of tissue factor pathway inhibitor (TFPI) Cosfroviximab ZMapp Chimeric monoclonal antibody IgG1κ Triple monoclonal antibody cocktail Disease modifying Ebola virus Ongoing studies show benefit but not enough enrolled to power study Ebola virus glycoprotein Crenezumab RG7412 MABT5102A Humanized monoclonal antibody IgG4 Disease modifying Alzheimer's disease phase III study ongoing prodromal/mild AD 2021 Phase III 2022 Intravenous 1-40-β-amyloid Crizanlizumab SelG1 FDA review possible 2019 Humanized monoclonal antibody IgG2κ Disease modifying Sickle cell disease phase II 2022 children Phase II adults decrease pain crisis Intravenous P Selectin Crotedumab Human monoclonal antibody IgG4κ Disease modifying DM type II No results GCGR Cusatuzumab ARGX-110 Humanized monoclonal antibody IgG1 Antineoplastic Phase I completed safe Phase I/II CTCL dec 2018 Nasopharyngeal carcinoma 2018 Intravenous CD70 Dacetuzumab HU-S2C6 ASKP1240 SGN-40 Humanized monoclonal antibody IgG1 Antineoplastic Hematologic cancers Multiple myeloma phase I 2007 Large B-cell lymphoma phase II 2009 enrollment stopped no benefit CLL phase II 2006 NHL phase I Renal transplant (CIRRUS I) phase II 2022 SLE nephritis phase II 2020 Intravenous CD40 Daclizumab Zenapax Zinbryta FDA 1997 EU 1999 Zenapax withdrawn from market Apr 2009 for commercial reasons Zinbryta withdrawal 2018 secondary to risk/benefit profile Humanized monoclonal antibody IgG1κ Disease modifying Prevention of organ transplant rejections Phase IV kidney transplants, multiple sclerosis phase III 2018 pulled from market secondary inflammatory brain disorders Biogen Heart transplant phase IV 108 studies Zanapax discontinued from market by Roche (basiliximab replace) CD25 (α chain of IL-2 receptor) Dalotuzumab Humanized monoclonal antibody IgG1κ Antineoplastic Phase I multiple Phase II breast no improvement × 2 Phase III colon no improvement Ped solid phase I Intravenous IGF-1 receptor (CD221) Dapirolizumab pegol Humanized monoclonal antibody IgG1κ SLE phase II Nov 2018 Phase I safe Intravenous CD154 (CD40L) Daratumumab Darzalex FDA 2015 EU 2016 Human IgG1κ Antineoplastic agent Multiple myeloma relapse/refractory Phase III completed Intravenous solution CD38 Induces CDC, ADCC, ADCP, and apoptosis Dectrekumab QAX576 Human monoclonal antibody IgG1κ Cancers, asthma phase II, idiopathic pulmonary fibrosis, eosinophilic Esophagitis phase II some benefit but primary endpoint not achieved, Keloids, Crohn's disease phase II trials 2013 Nothing on PubMed Substance is registered with FDA, creative lab IL-13 Demcizumab Humanized monoclonal antibody IgG2κ Antineoplastic NSCLC phase II 2018 Phase I safety established with 50% tumor regression response Intravenous Delta-like ligand 4DLL4 DLL4 and Notch1, signaling stimulated by DLL4 plays a role in development of blood vessels throughout life Denintuzumab mafodotin HBU-12 SGN-CD19A Humanized monoclonal antibody IgG1κ Antibody-drug conjugate (ADC) composed of a humanized anti-CD19 monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) Antineoplastic LBCL phase II terminated study by company Acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma Phase I 2017 Phase II 2018 terminated by sponsor Intravenous CD19 Denosumab AMG162 Prolia FDA 2010 EU 2010 Xgeva FDA 2011 EU 2011 Human monoclonal antibody IgG2 Disease modifying Osteoporosis FREEDOM trial, bone metastases, etc. 186 studies Phase III completed Melanoma phase II 2022 Bone giant cell tumor phase II 2025 Subcutaneous Receptor activator of nuclear factor kappa-B ligand (RANKL) Xgeva: Prevention of skeletal-related events (SREs) in adults with bone metastases from breast and castration-resistant prostate cancer. Prolia: Osteoporosis Depatuxizumab mafodotin ABT 414 Chimeric humanized monoclonal antibody IgG1κ CONJUGATED TO AURISTATIN F Glioblastoma Phase III Nov 2019 Children phase III 2020 Intravenous EGFR Derlotuximab biotin Iodine (131 I) derlotuximab biotin Chimeric monoclonal antibody IgG1κ Immunoassays Potential for glioblastoma multiforme Histone complex Detumomab Murine monoclonal antibody IgG1 Antineoplastic B-lymphoma cell Nothing on PubMed or clinical trials Substance is not registered with FDA, is on creative lab CD3E Dezamizumab GSK-2398852 Humanized monoclonal antibody IgG1κ Disease modifying Treat amyloidosis Transthyretin cardiomyopathy amyloidosis (ATTR-CM), suspended pending data review Aug 2018 phase I x 4 Intravenous Serum amyloid P component Dinutuximab APN311 Unituxin FDA 2015 EU 2015 then withdrawn EU Chimeric monoclonal antibody IgG1κ Antineoplastic Neuroblastoma phase I 2022 SCLC phase III Nov 2019 Osteosarcoma phase II Dec 2018 Neuroblastoma phase II 2020 Intravenous GD2 ganglioside Diridavumab CR6261 Human monoclonal antibody IgG1λ Disease modifying Infectious disease/influenza A Very good response in animal study mice Phase II 2019 Intravenous Influenza A hemagglutinin Domagrozumab PF-06252616 Humanized monoclonal antibody IgG1κ Disease modifying Duchenne muscular dystrophy phase II 2018 Phase I completed GDF-8 Dorlimomab aritox F(ab') 2 Murine Nothing on PubMed or clinical trials Substance is not registered with FDA, or creative lab Dostarlimab TSR042 WBP285 FDA review pending 2019 Humanized monoclonal antibody IgG4κ Antineoplastic Solid tumor Phase I, II, III studies ongoing Ovarian CA (first study) phase III 2023 Programmed cell death protein-1 (CD279) PCDP1 Drozitumab PRO95780 rhuMAB DR5 Human monoclonal antibody IgG1λ Antineoplastic Colorectal cancer Ib 2012 Preclinical rhabdomyosarcoma 2018 Chondrosarcoma not efficacious NHL results? Intravenous Death receptor 5 (DR5) Duligotuzumab MEHD7945A Human monoclonal antibody IgG1κ Antineoplastic squamous head and neck phase II no benefit Colon ca phase II no benefit Anti-EGFR × Anti-HER3 bispecific antibody Dupilumab Dupixent FDA 2017 Human monoclonal antibody IgG4 Disease modifying asthma, atopic dermatitis Ongoing studies Subcutaneous IL4 Durvalumab Imfinzi FDA 2017 Human monoclonal antibody IgG1κ Antineoplastic agent Treat NSCLC stage III phase I, urothelial carcinoma Intravenous PD-L1 (CD274) and CD80—inhibit binding of programmed death ligand 1 to PD-1 and CD80 allowing T cell to recognize and kill tumor cells Dusigitumab MEDI 573 Human monoclonal antibody IgG2λ Antineoplastic Breast cancer phase II results? HCC phase II results? Intravenous ILGF2 Duvortuxizumab MGD011 Chimeric/humanized monoclonal antibody Antineoplastic B-cell malignancy Phase I/II Jul 2018/2020 Intravenous CD19, CD3E Ecromeximab KW2871 Chimeric monoclonal antibody IgG1κ Antineoplastic Metastatic melanoma Phase I/II clinical activity limited Intravenous GD3 ganglioside Eculizumab Soliris PNH FDA 2007 EU 2007 aHUS, and myasthenia gravis FDA 2018 EU 2018 Japan 2018 Humanized monoclonal antibody IgG1/4 Immuno-regulation Paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (HUS ) Generalized myasthenia gravis (MG) Phase II CAD Intravenous C5 Edobacomab E5 Murine monoclonal antibody No improved survival Endotoxin Edrecolomab Panorex Murine monoclonal antibody IgG2κ Antineoplastic Colorectal carcinoma phase III 2003 no improvement Intravenous Glycoprotein EpCAM/17-1A Efalizumab Raptiva FDA 2003 EU 2004 Withdrawn both markets 2009 Recombinant humanized monoclonal antibody IgG1κ Disease modifying (2003 approved) psoriasis Subcutaneous Voluntary withdrawal 2009 Human CD11a Increase risk progressive multifocal leukoencephalopathy (PML) Efungumab MYC123 Mycograb Mycograb C28Y Human scFv Antiinfectious agent Invasive Candida infection Intravenous Heat shock protein 90 (Hsp90) Eldelumab Mdx 1100 Human monoclonal antibody IgG1κ Crohn's disease phase IIa no significant response, ulcerative colitis phase IIb prim endpoint not achieved Rheum arthritis phase II Intravenous Interferon γ-induced protein CXCL 10 Elezanumab PR-1432051 ABT-555 Human monoclonal antibody IgG1λ Spinal cord injury and multiple sclerosis phase II 2021 Intravenous REPULSIVE GUIDANCE MOLECULE FAMILY MEMBER A (RGMA) Elgemtumab LJM716 Human IgG1κ Antineoplastic Breast gastric phase I Intravenous ERBB3 (HER3) Elotuzumab PDL063 Empliciti FDA 2015 EU 2016 Human IgG1κ Antineoplastic Multiple myeloma Phase III completed and ongoing Intravenous SLAMF7 Elsilimomab B-E8 Humanized monoclonal antibody IgG1 Antineoplastic multiple myeloma Not effective in mice IL-6 Emactuzumab RG7155 Humanized monoclonal antibody IgG1 ANTINEOPLASTIC Phase I 2019 solid tumors Phase II 2025 REDIRECT study ovarian, fallopian tube cancer Pancreatic phase II 2020 HUMAN MACROPHAGE COLONY-STIMULATING FACTOR RECEPTOR (CSF1R, CD115) Emapalumab NI-0501 Gamifant FDA 2018 EU pending Human monoclonal antibody IgG1λ Hemophagocytic lymphohistiocytosis Phase III 2021 Intravenous Interferon γ Emibetuzumab LA480 LY2875358 Humanized monoclonal antibody IgG4κ Bivalent antibody Antineoplastic NSCLC phase II 2020 Advanced cancer Gastric safe ?effective adenocarcinoma Gastroesophageal junction adenocarcinoma Hepatocellular cancer Renal cell carcinoma Nonsmall cell lung cancer phase II Jan 2018 Phase I safe with tumor response Intravenous Hepatocyte growth factor receptor (HHGFR) and MET signaling Emicizumab ACE910 Hemlibra FDA 2018 Humanized monoclonal antibody IgG4κ Bispecific Disease modifying Hemophilia A phase III 2020 With or without inhibitors Subcutaneous Activated F9, F10 Enapotamab vedotin Human monoclonal antibody IgG1κ Antineoplastic Nothing on PubMed or clinical trials Substance is not registered with FDA, or creative lab Human growth factor receptor AXL Enavatuzumab PDL192 Humanized monoclonal antibody IgG1κ Antineoplastic Phase I 2011 No responses and liver pancreatic toxicity Intravenous TWEAK receptor Enfortumab vedotin FDA review pending 2019 Human monoclonal antibody Antineoplastic bladder cancer phase I Phase II ongoing Nectin-4 Anti-Nectin-4 Monoclonal antibody attached to a microtubule-disrupting agent, monomethyl auristatin E (MMAE) Enlimomab pegol Murine monoclonal antibodyIgG2a Disease modifying Stroke Nothing on PubMed or clinical trials Substance is not registered with FDA ICAM-1 (CD54) Enoblituzumab MGA 271 Humanized monoclonal antibody IgG1κ Antineoplastic Phase I 2022 children Neuroblastoma Rhabdomyosarcoma Osteosarcoma Ewing sarcoma Wilms tumor Desmoplastic small round cell tumor Phase I melanoma, NSCLC 2018 Phase II prostate 2021 CD276 (B7–H3) Enokizumab MEDI528 Humanized monoclonal antibody IgG1κ Asthma phase II No improvement Intravenous IL9 Enoticumab REGN421 Human monoclonal antibody IgG1κ Antineoplastic Phase 1 2014 ovarian cancer + Delta-like canonical notch ligand 4 (DLL4) Ensituximab NEO-201 NPC-1C Chimeric monoclonal antibody IgG1κ Antineoplastic Phase II pancreatic and colorectal cancer 2017 Intravenous 5AC Enterecept RHU-TNFR:FC Enbril FDA 2003 1-235-Tumor necrosis factor receptor fusion protein attached to recombinant human IgG1 Fc fragment Disease modifying Antirheumatic drug Not effective for inflammatory bowel disease Subcutaneous TNFα Epitumomab cituxetan AS-1402 HuHMFG-1 Sontuzumab Humanized monoclonal antibody IgG1 Antineoplastic Breast cancer phase II 2012 no benefit Episialin MS4A1 (membrane-spanning 4-domains subfamily A member 1, CD20 (HMFG-1) Epratuzumab HLL2 AMG412 Humanized monoclonal antibody IgG1κ ADCC/CDC Antineoplastic B-ALL phase III ongoing 2018 Disease modifying SLE phase III no improvement Intravenous CD22 Eptinezumab ALD403 FDA review possible 2019 Monoclonal antibody IgG1κ Disease modifying Migraine phase III Calcitonin gene-related peptide Erenumab Aimovig FDA May 2018 Human monoclonal antibody IgG2λ Disease modifying Migraine phase III Calcitonin gene-related peptide (CGRP) Erlizumab Rhumab CD18 Humanized IgG1 F(ab') 2 fragment Antineoplastic (lab tests) Immunosuppressive drug phase I study cough up blood and phase II did not meet goals Heart attack, stroke, traumatic shock ??no successful CD18 drug to date LGL type leukemia ITGB2 (CD18) and LFA-1 block growth factor of blood vessels stop lymphocytes from moving into inflamed tissue Ertumaxomab Rexomun Rat/murine hybrid triomab, murine IgG2a HET2 target, RAT IgG2bλ CD3 target Antineoplastic Breast Gastric, esophageal Phase II studies terminated company to focus on other plans not safety concerns concentrate on catumaxomab Phase I found safe 2016 Intravenous HER2/neu, CD3 Etaracizumab or etaratuzumab MEDI-522 Abegrin Vitaxin Humanized monoclonal antibody IgG2κ Antineoplastic Melanoma phase II 2010 not beneficial, prostate cancer, ovarian cancer small and large bowel cancer phase I and II completed results unreported 2017 Intravenous Integrin αvβ3 Etigilimab Humanized monoclonal antibody IgG1κ Nothing on pubmed or clinical trials Substance is registered with FDA, or is not in creative lab TIGIT T-cell immunoreceptor with Ig and ITIM domains Etrolizumab PRO145223 RHUMAB BETA7 Humanized monoclonal antibody IgG1κ Disease modifying Inflammatory bowel disease UC phase III 2020 × 4/2023/2024/2025 Crohn phase III 2021 Subcutaneous Integrin β7 Inhibits binding of αEβ7 to E-cadherin Evinacumab REGN1500 Human monoclonal antibody IgG4κ Disease modifying Dyslipidemia Phase II 2020 Phase III 2020/2022 Angiopoietin 3 Evolocumab Repatha FDA 2015 EU 2015 Human monoclonal antibody IgG2λ Disease modifying hypercholesterolemia Completed phase III Heterozygous familial hypercholesterolemia, CVD Subcutaneous Proprotein convertase subtilisin kexin type 9 (PCSK9) Exbivirumab Humanized monoclonal antibody IgG1λ Disease modifying prevent disease Hep B Oral therapy Abstract of randomized study of 50 patients Hepatitis B surface antigen Fanolesomab RB5-IGM NeutroSpec Murine monoclonal antibody Diagnostic imaging Appendicitis (diagnosis only) CD15 Faralimomab Murine monoclonal antibody IgG1 Nothing on PubMed or clinical trials Substance is not registered with FDA, or is not in creative lab Interferon receptor Faricimab RG7716 RO6867461 Humanized monoclonal antibody IgG1mab Disease modifying angiogenesis, ocular vascular diseases STAIRWAY, BOULEVARD, RHINE, Yosemite phase II and III studies phase III 2022 for diabetes maculae edema AMD LUCERNE phase III 2022 TENAYA phase III 2022 Intravitreous ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR/ANTIANGIOPOIETIN 2 BISPECIFIC ANTIBODY (VEGF-A and Ang-2) Farletuzumab MORAB-003 Humanized monoclonal antibody IgG1κ Antineoplastic Ovarian cancer phase III subgroup may benefit Intravenous Folate receptor 1 Fasinumab REGN475 SAR164877 MT5547 Human monoclonal antibody IgG4κ Disease modifying acute sciatic pain phase III Knee arthritis pain phase III 2021 Subcutaneous (auto injector) Human nerve growth factor (HNGF) FBTA05 Bi20 Lymphomun Rat IgG2b (CD3)/murine IgG2a (CD20) hybrid trifunct Antineoplastic Chronic lymphocytic leukemia trial terminated recruitment too slow Intravenous? CD20/CD3 Felvizumab Humanized monoclonal antibody IgG1κ Antiinfectious agent Respiratory syncytial virus infection Nothing on PubMed or clinical trials Substance is not registered with FDA, but is in creative lab Respiratory syncytial virus Fezakinumab Human monoclonal antibody IgG1λ Disease modifying Rheumatoid arthritis, psoriasis (not good for) Atopic dermatitis phase IIb good results Intravenous IL-22 Fibatuzumab Ifabotuzumab Humanized monoclonal antibody IgG1κ Disease modifying Myelodysplastic syndrome Research in Australia for GBM phase I Ephrin receptor A3 Ficlatuzumab SCH 900105 AV 299 Humanized monoclonal antibody IgG1κ Antineoplastic Head and neck cancer phase I 2020 Pancreatic phase I 2023 NSCLC phase I/II 2013 AML phase I 2020 Intravenous Hepatocyte growth factor (HGF) hepapoietin A Figitumumab CP751871 Human monoclonal antibody IgG2κ Ceased development in 2011 by pfizer Antineoplastic Adrenocortical carcinoma, nonsmall cell lung carcinoma etc. ?additional benefit in phase I Insulin-like growth factor receptor IGF-1 receptor (CD221) Firivumab Human monoclonal antibody IgG1κ Disease modifying Influenza A virus hemagglutinin Nothing on PubMed or clinical trials Substance is registered with FDA, and is in creative lab INFLUENZA A VIRUS HEMAGGLUTININ HA Flanvotumab IMC20D7S Human monoclonal antibody IgG1κ Antineoplastic Melanoma phase I 2012 Intravenous No published data TYRP1 (glycoprotein 75) Fletikumab Human monoclonal antibody IgG4 Disease modifying Rheumatoid arthritis phase IIa good, phase IIb no results IL 20 Flotetuzumab MGD006 S80880 Humanized di-scFv dual affinity retargeting (DART) to CD123 and CD3 Antineoplastic Hematologic malignancies (ALL, NHL) Phase II not yet recruiting 2018 Intravenous? IL 3 receptor Fontolizumab HuZAF Humanized monoclonal antibody IgG Disease modifying Treat Crohn's clinical development stopped despite some benefit phase II ustekinumab is better IFN-γ FOR46 Antibody drug conjugate Antineoplastic Phase I for multiple myeloma failed remission or relapse Phase I prostate cancer Intravenous CD46 Foralumab Human monoclonal antibody IgG1κ Disease modifying NASH phase II 2019 Oral CD3 epsilon Foravirumab Human monoclonal antibody IgG1κ Disease modifying rabies (prophylaxis) Nothing in pub med or clinical trials Rabies virus glycoprotein Fremanezumab LBR-101 RN307 Ajovy FDA 2018 Humanized monoclonal antibody IgG2κ Disease modifying migraine and cluster headache phase III 2019 Subcutaneous α-Calcitonin gene-related peptide Fresolimumab Humanized monoclonal antibody IgG4 Disease modifying Idiopathic pulmonary fibrosis (IPF), scleroderma, focal segmental glomerulosclerosis (phase 2), cancer (kidney cancer and melanoma) Need larger study for FSGS Good response scleroderma https://newdrugapprovals.org/2016/01/30/fresolimumab/ TGF β 1 Frovocimab LY3015014 Humanized monoclonal antibody IgG4κ Disease modifying hypercholesterolemia Completed phase II trials 2014 good response and safe Subcutaneous PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 (PCSK9) Frunevetmab https://en.wikipedia.org/wiki/List_of_therapeutic_monoclonal_antibodies - cite_note-WHOList 116-17 NV-02 Veterinary monoclonal antibody IgG1κ Veterinary Feline muscle nerve growth factor Fulranumab AMG403 Human monoclonal antibody IgG2κ Disease modifying Pain osteoarthritis pain phase III 2017 Subcutaneous Nerve growth factor Galcanezumab LY2951742 Emgality FDA 2018 Humanized monoclonal antibody IgG4κ Disease modifying Migraine Phase III completed Cluster HA phase III 2020 Subcutaneous Calcitonin gene-related polypeptides (CGRPs) α and β Galiximab IDEC-114 Chimeric monoclonal antibody IgG1λ ADCC/CDC Antineoplastic lymphoma phase II 2015 minimal response ORR 10.3% Intravenous CD80 Gancotamab MM-302 Human cFv Single chain fragment Antineoplastic Breast cancer phase I–III Intravenous HER2/neu Ganitumab AMG479 Human monoclonal antibody IgG1κ Antineoplastic Pancreatic phase III—no increase benefit Phase III for rhabdomyosarcoma and Ewings 2021 Not beneficial in NSCLC Intravenous IGF-1 receptor (CD221) Gantenerumab R04909832 R1450 Human monoclonal antibody IgG1κ Disease modifying Alzheimers Phase III stopped for potential futility additional studies at higher dosing (DIAN in a phase II/III trial in individuals at risk For and with early-stage autosomal-dominant AD phase III 2021 Subcutaneous Beta amyloid Gatipotuzumab PankoMab-GEX Humanized monoclonal antibody IgG1κ Antineoplastic Ovarian, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC), gynecological cancers (GYN) phase I used for diag/prog now Intravenous Musculus, antimucin (MUC1) Gavilimomab ABX-CBL Murine monoclonal antibody IgM Disease modifying Graft versus host disease phase III completed 2005 less effective than antithymocyte antibody CD147 (basigin) Gedivumab RG7745 RO6876802 Human monoclonal antibody IgG1κ Disease modifying Influenza virus A No studies PubMed/clinical trials Influenza virus hemagglutinin HA Gemtuzumab ozogamicin Mylotarg AML FDA 2000 Voluntary withdrawal 2010 VOD now black box warning Returned to market with FDA approval 2017 Humanized monoclonal antibody IgG4/toxin conjugate Antineoplastic Acute myelogenous leukemia Many ongoing and completed studies Intravenous CD33 Gevokizumab XOMA 052 Humanized monoclonal antibody IgG2κ Disease modifying DM phase II (late stage) no results Other dz too 24 studies behcet uveitis failed primary end point phase III (Eyeguard _B) 2015 Subcutaneous IL-1β Gilvetmab PD1 Veterinary monoclonal antibody IgG2κ Antineoplastic No studies clinical trial, pub med CANIS FAMILIARIS PROGRAMMED CELL DEATH PROTEIN 1 (PCDC1) Gimsilumab MORAb-022 Human monoclonal antibody IgG1 Disease modifying Rheumatoid arthritis Asthma Phase I poster presentation of safety results good 2016 Intravenous HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (CSF2) Girentuximab WX-G250 CG250 Rencarex Reductane Chimeric monoclonal antibodyIgG1κ Radioactive labeled ab Antineoplastic Clear cell renal cell carcinoma for treatment and imaging Intravenous Carbonic anhydrase 9 (CA-IX) Glembatumumab vedotin CR011 Human monoclonal antibody IgG2κ Antibody drug complex Antineoplastic Melanoma phase II, breast cancer Intravenous Human glycoprotein NMB extracellular domain (GPNMB) Golimumab CNTO 148 Simponi FDA 2009 EU 2009 Human monoclonal antibody IgG1κ Disease modifying Rheumatoid arthritis, psoriatic arthritis , juvenile rheum arth, ankylosing spondylitis many studies, UC, DM1 phase I (2020, 2021) Subcutaneous, intravenous TNF-α Gomiliximab IDEC-152 Lumiliximab ST-152 Chimeric monoclonal antibody IgG1κ ADCC/CDC Allergic asthma ? Antineoplastic CLL Phase I, phase 2/3 2014 Failed efficacy CD23 (IgE receptor) Gosuranemab BIIB092 IPN-007 FDA orphan drug status Humanized monoclonal antibody IgG4κ Progressive supranuclear palsy Phase I 2020 Alzheimer 2021 Intravenous τ protein Guselkumab CNTO 1959 Tremfya FDA ? Human monoclonal antibody IgG1λ Disease modifying Psoriasis Adenomatous polyposis Subcutaneous IL23A Hu3F8 Humanized monoclonal antibody IgG3 Antineoplastic Phase I For neuroblastoma mod tox and substantial effect on tumor Phase II ongoing Intravenous GD2 ganglioside Ianalumab Human monoclonal antibody IgG1κ Immunomodulation Autoimmune hepatitis Human cytokine receptor BAFF-R Ibalizumab Trogarzo FDA/EU approved Humanized monoclonal antibody IgG4 Disease modifying anti-HIV Phase III CD4 Ibritumomab tiuxetan IDEC-129 IDEC-IN2B8 IDEC-Y2B8 Zevalin FDA 2002 EU 2004 Murine monoclonal antibody IgG1κ YT 77 or In 98 bound Antineoplastic Follicular non-Hodgkin's lymphoma , B-cell NHL , multiple myeloma conditioning for BMT, B-cell DLCL, mantle cell Many studies CD20 (human B-lymphocyte-restricted differentiation antigen, Bp35) Icrucumab IMC 18F1 Human monoclonal antibody IgG1κ Antineoplastic No benefit breast phase II No benefit colon phase II No benefit urothelial phase II Intravenous Vascular endothelial growth factor receptor (VEGFR-1) Idarucizumab Praxbind FDA 2015 EU 2015 Humanized monoclonal antibody Fab fragment Antidotes Drug reversal agent Reversal of anticoagulant effects of dabigatran Phase III trial RE-VERSE AD Intravenous Dabigatran etexilate Igovomab Indimacis-125 Murine F(ab') 2 Diagnostic imaging Ovarian cancer (diagnosis) Iladatuzumab vedotin RG7986 Humanized monoclonal antibody IgG1κ Antineoplastic Nothing in PubMed or clinical trials Human gene B29 protein (CD97B) Imalumab BAX69 Human monoclonal antibody IgG1κ Antineoplastic Intraperitoneal infusion, intravenous Macrophage migration inhibitory factor (MIF) Imaprelimab Humanized IgG1κ Antineoplastic Nothing in PubMed or clinical trials Melanoma cell adhesion molecule (MCAM) Imciromab pentetate Myoscint FDA approved 1996 Withdrawn from market Murine monoclonal antibody fragment Fab IgG2aκ Diagnostic Cardiac imaging Cardiac myosin Imgatuzumab RG7160 RO5083945 GA201 HUMA-B Humanized monoclonal antibody IgG1κ Antineoplastic Colorectal 2013 Head and neck 2017 NSCLC 2017 Epidermal growth factor receptor (EGFR, HER1) IMGN632 Monoclonal antibody with antibody drug conjugate Antineoplastic AML, ALL phase I 2021 NCT03386513 Intravenous CD123 Inclacumab RG1512 RO4905417 Human monoclonal antibody IgG4κ Disease modifying Cardiovascular disease phase II Intravenous Selectin P Indatuiximab ravtansine Chimeric monoclonal antibody IgG4κ Antineoplastic Preclinical breast cancer CD138 (syndecan-1) SDC1 Indusatumab vedotin TAK-264 MLN0264 Human monoclonal antibody IgG1κ conjuagated via a mc-val-cit-PABC linker to monomethyl auristatin E {MMAE (5F9-mc-val-cit-PABC-MMAE)} Antineoplastic Gastrointestinal, pancreatic, gastroesophageal Safe phase I, phase II pancreatic min response, three studies terminated by company business Intravenous Guanylate cyclase C (GUCY2C) Inebilizumab MEDI-551 Humanized monoclonal antibody IgG2κ ADCC Antineoplastic Refractory DLBCL phase II 2016 Disease modifying systemic sclerosis, multiple sclerosis Neuromyelitis optica Intravenous CD19 Infliximab Remicade FDA 1998 EU 1999 Inflectra FDA 2016 EU 2013 Remsima EU 2013 Human-murine chimera IgG1κ Human constant, murine variable region Disease modifying Remicade Crohn's disease; ulcerative colitis; rheumatoid arthritis; ankylosing spondylitis; psoriatic arthrits; plaque psoriasis Inflectra Spondylitis; ankylosing; arthritis; rheumatoid colitis; ulcerative arthritis; psoriatic Crohn's disease; psoriasis Remsima Spondylitis; ankylosing arthritis; rheumatoid colitis; ulcerative Crohn's disease; arthritis; psoriatic psoriasis Intravenous solution TNF-α Inolimomab Murine monoclonal antibody Disease modifying GVHD phase III No better than ATG in 3 studies Abandoned not in 2017 Cochrane review CD25 (α chain of IL-2 receptor) Inotuzumab ozogamicin G544 Besponsa FDA 2017 Humanized monoclonal antibody IgG4κ ADCC/CDC Antineoplastic ALL phase II 2023 Multiple other studies Intravenous CD22 Intetumumab CNTO095 Human monoclonal antibody IgG1κ Antineoplastic Solid tumors (prostate cancer, melanoma) Melanoma phase II possible benefit 2011 Prostate cancer no additional benefit 2013 phase II Intravenous CD51 Ipilimumab Yervoy FDA 2011 EU 2011 Human monoclonal antibody IgG1κ Antineoplastic agent Bladder carcinoma (trials ongoing) Melanoma Ipilimumab MDX010 MDX101 BMS-734016 Yervoy FDA 2011 melanoma Metastatic renal cancer/colorectal cancer 2018 Human monoclonal antibody IgG1κ Antineoplastic Melanoma (checkmate 067) Renal cell carcinoma (checkmate 214) Colorectal cancer Pancreatic? Intravenous CD152 cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and blocks interaction with its ligands CD80/CD86 Iratumumab MDX060 Human monoclonal antibody IgG1κ Antineoplastic Hodgkin's lymphoma phase II completed Clinical research discontinued 2009 Intravenous CD30 (tumor necrosis factor receptor superfamily, Member 8; TNFRSF8) aka Ki-1 Ag Isatuximab SAR650984 FDA review possible 2019 Chimeric monoclonal antibody IgG1κ Antineoplastic multiple myeloma Phase I 2019 Phase II 2022 Phase III 2025 Intravenous CD 38 Iscalimab CFZ533 Human monoclonal antibody IgG1κ Disease modifying Potential treat autoimmune disease Lupus nephritis phase II 2020 Myasthenia gravis GVHD Kidney transplant 2022 phase II Preclinicals Intravenous CD40 Istiratumab MM-005 MM-141 Human monoclonal antibody IgG1 Antineoplastic Advanced solid tumors Pancreatic cancer phase II 2018 Insulin-like growth factor I receptor/neuregulin receptor HER3 (IGF1R, CD221) Itolizumab Alzumab FDA Humanized monoclonal antibody IgG1κ Disease modifying Psoriasis GVHS phase II 2022 CD6 Ixekizumab Taltz Humanized monoclonal antibody Disease modifying Phase III radiographic axial spondyloarthritis Psoriatic arthritis Subcutaneous IL 17A Keliximab Became clenoliximab IgG4 Chimeric monoclonal antibody IgG1λ Disease modifying Chronic asthma Rheumatoid arthritis CD4 Labetuzumab hMN14 CEA-Cide Humanized monoclonal antibody IgG1 Antineoplastic Colorectal cancer Gastrointestinal phase II 2021imagin Phase II completed therapy 2003 Intravenous CEA Lacnotuzumab MCS110 Humanized monoclonal antibody IgG1κ Antineoplastic Breast, pigmented villonodular synovitis (PVNS) Squam ESOP phase II 2024 Gastric 2019 CSF1, MCSF Ladiratuzumab vedotin Humanized monoclonal antibody IgG1κ Antibody drug conjugate Antineoplastic Phase I triple-negative breast cancer 2017 ongoing study LIV-1 Lampalizumab RG7417 Humanized monoclonal fragment IgG1κ Disease modifying Geographic atrophy secondary to age-related macular degeneration phase III Jan 2018 ineffective Intravitreous Complement factor D (CFD) Lanadelumab SHP643 DX-2930 Takhzyro FDA 2018 Human monoclonal antibody IgG1κ Disease modifying Angioedema phase III 2019 Subcutaneous Kallikrein (KLKB1) Landogrozumab LY2495655 Humanized monoclonal antibody IgG4κ Disease modifying Muscle wasting disorders, i.e., after hip surgery phase II Pancreatic cancer phase II no benefit cancer, some muscle improvement but primary objective not met Intravenous Subcutaneous Human growth differentiating factor 8 (GDF-8) aka myostatin (MSTN) Laprituximab emtansine IMGN289 Chimeric monoclonal antibody No trials or PubMed or creative lab only in FDA registry ?new EGFR Larcaviximab ZMAPP Chimeric monoclonal antibody IgG1κ Disease modifying Ebola virus No studies clinical trial or PubMed Ebolavirus glycoprotein Lebrikizumab MILR1444A TNX-650 RG-3637 PRO301444 Humanized monoclonal antibody IgG4κ Disease modifying Asthma phase III Atopic dermatitis HL phase II 2007 Subcutaneous injection Interleukin-13 (IL-13) Lemalesomab Murine monoclonal antibody IgG1κ Diagnostic agent NCA-90 (granulocyte antigen) Lendalizumab Olendalizumab ALXN-1007 Humanized monoclonal antibody IgGκ Disease modifying Antiphospholipid syndrome GI GVHD Intravenous Anticomplement 5A Lenvervimab Humanized IgG1κ Disease modifying Hepatitis B No studies in clinical trials or PubMed Hepatitis B surface antigen Lenzilumab KB-003 Human monoclonal antibody Antineoplastic chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia phase I Intravenous GRANULOCYTEMACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) Lerdelimumab CAT-152 Trabio Human monoclonal antibody IgG4 Disease modifying Phase I studies ?Cancer and fibrosis Trials stopped for fibrosis after glaucoma surgery Transforming growth factor β 2 Leronlimab PRO-140 FDA review 2018 Humanized IgG4κ Disease modifying HIV phase III ongoing no results published good results phase II Subcutaneous Chemokine receptor 5 (CCR5) Lesofavumab RG70026 Human monoclonal antibody IgG1κ Disease modifying Influenza A No studies clinical trials or PubMed Hemagglutinin HA Letolizumab Humanized synthetic light chain variable region (scFv) Disease modifying inflammatory diseases No studies clinical trials or PubMed or creative labs TRAP Lexatumumab HGS1018 HGS-ETR2 Human monoclonal antibody IgG1λ Antineoplastic Breast Pancreatic Intravenous Tumor necrosis factor receptor superfamily member 10B/death receptor 5 (TRAIL-R2) Libivirumab Humanized monoclonal antibody IgG1κ Antiinfectious Prevent disease Hep B Oral therapy Abstract of randomized study of 50 patients Hepatitis B surface antigen Lifastuzumab vedotin DBNIB0600A Humanized monoclonal antibody Antineoplastic Ovarian cancer Phase 2 Intravenous Phosphate-sodium cotransporter Ligelizumab QGE031 Humanized monoclonal antibody IgG1κ Disease modifying SSevere asthma and chronic spontaneous urticaria phase II and III ongoing trial 2021 Subcutaneous Immunoglobulin E (IGHE) Lilotomab satetraxetan Betalutin Murine monoclonal antibody IgG1 Antineoplastic NHL 2020/phase II 2025 Diffuse lg B-cell lymphoma 2019 CD37 Lintuzumab SGN33 Humanized monoclonal antibody IgG1κ Antineoplastic AMLphase I/II 2022 Mult myeloma phase I 2020 Myelodysplastic phae II 2011 Intravenous CD33 Lirilumab IPH2102 Human monoclonal antibody IgG4 Antineoplastic Solid and hematological cancers No good aml, squam cell head neck no good, bladder cancer ongoing? May benefit MDS Intravenous Killer cell immunoglobulin like (KIR2D) Block the interaction between KIR2DL-1,-2,-3 inhibitory receptors and their ligands Lodelcizumab LFU720 Humanized monoclonal antibody IgG1κ Disease modifying Hypercholesterolemia Unknown studies in clinical trials and PubMed Proprotein convertase subtilisin/kexin type 9 (PCSK9) Lokivetmab Cytopoint FDA approved for dogs only Canis monoclonal antibody IgG2κ Disease modifying Veterinary Clinical signs of atopic dermatitis in dogs Canis lupus familiaris IL31 Loncastuximab tesirine ADCT-402 Chimeric monoclonal antibody IgG1κ Antineoplastic Diffuse large B-cell lymphoma phase II 2020 Intravenous CD19 Lorvotuzumab mertansine BB-10901 IMGN901 Humanized monoclonal antibody IgG1κ Antineoplastic SCLC Ovarian AML phase II Wilm, rhabdomyosarcoma, Neuroblast, MPNST, Synovial sarcoma 2018 phase II Intravenous CD56 Losatuxizumab vedotin ABBV-221 Chimeric/humanized monoclonal antibody IgG1 Antineoplastic Epidermal growth factor (EGRF, ERBB1 HER1) Lucatumumab HCD122 Discontinued development by Novartis 2013 Human monoclonal antibody IgG1κ Antineoplastic Multiple myeloma, non-Hodgkin's lymphoma, Hodgkin's lymphoma Intravenous CD40 Lulizumab pegol Humanized monoclonal antibody Disease modifying SLE Phase I safe Phase II no response Intravenous Subcutaneous CD28 Lumretuzumab RG7116 RO5479599 Humanized monoclonal antibody IgG1κ Antineoplastic Intravenous CD28; receptor for tyrosine-protein kinase(erbB-3, HER3) Lupartumab amadotin BAY-1129980 Human monoclonal antibody IgG Antineoplastic Phase I terminated Why? Intravenous GPI- anchored cell surface-associated protein C4.4A (LYPD3) Lutikizumab ABT981 Humanized monoclonal antibody Disease modifying Osteoarthritis Phase IIa no effect Subcutaneous Interleukin 1 alpha/interleukin 1 beta Mapatumumab HGS1012 Human monoclonal antibody IgG4λ Antineoplastic Hepatocellular no benefit Multiple myeloma Cervical cancer NSCLC no benefit NHL Bladder cancer may be beneficial Tumor necrosis factor receptor superfamily member 10A; cytokine receptor DR4 (death receptor 4 tumor necrosis receptor apoptosis-induced ligand (TRAIL-R1) Margetuximab MGAH22 Chimeric/Humanized monoclonal antibody IgG1κ Antineoplastic Breast cancer Gastric cancer/GEC phase Ib/II trial Intravenous erbB2/HER2 Marstacimab PF-06741086 Human monoclonal antibody IgG1λ Disease modifying Bleeding with hemophilia phase II 2020 Subcutaneous Tissue pathway factor inhibitor (TFPI) Maslimomab Murine monoclonal antibody Immunosuppressive Unknown no studies and not listed in creative lab or FDA T-cell receptor Matuzumab EMD 72000 Humanized monoclonal antibody IgG1κ Antineoplastic Colorectal, lung and stomach cancer weakly beneficial Intravenous Epidermal growth factor receptor (EGFR) Mavrilimumab CAM3001 Human monoclonal antibody IgG4λ Disease modifying rheumatoid arthritis phase IIb good Subcutaneous GMCSF receptor α-chain MEDI565 MT111 AMG211 Fab IgG1 BiTE Antineoplastic Gastrointestinal adenocarcinoma phase I 2018 Intravenous CD3 and CEA Mepolizumab SB-240563 Bosatria Nucala FDA 2015 EU 2015 Human monoclonal IgG1κ Disease modifying No benefit in eosinophilic esophagitis Beneficial allergic severe asthma Subcutaneous Interleukin-5 (IL-5) antagonist Metelimumab CAT 192 Humanized monoclonal antibody IgG4 Disease modifying Scleroderma Dropped from further development TGF β 1 Milatuzumab HLL1 IMMU-115 Humanized monoclonal antibody IgG1κ Antineoplastic Multiple myeloma Lupus Leukemia Intravenous CD74 Minretumomab MOAB CC49 Murine monoclonal antibody IgG1 Diagnostic Tumor detection/diagnostic/prognostic Failed phase I clinical trials Tumor-associated glycoprotein 72 (TAG-72) Mirikizumab LY3074828 Humanized monoclonal antibody Disease modifying Psoriasis phase III 2020 UC phase III 2023 LUCENT 1 2021 phase III LUCENT 2 2022 Intravenous IL23A Mirvetuximab soravtansine M9346A IMGN853 Chimeric monoclonal antibody IgG1 Antineoplastic Ovarian phase III 2019 Breast ca phase II 2020 Intravenous Folate receptor alpha Mitumomab BEC-2 Murine monoclonal antibody Antineoplastic SCLC phase III no benefit 2005 GD3 ganglioside Modotuximab 1024 DS Zatuximab Futuximab SYM004 Chimeric monoclonal antibody IgG1κ Antineoplastic Antineoplastic Colorectal Phase 2019 Phase III 2025 Subcutaneous EGFR extracellular domain III/HER1 Mogamulizumab AMG761 KM8761 Poteligeo FDA 2018 Humanized monoclonal antibody IgG1κ Antineoplastic Adult T-cell leukemia/lymphoma Solid tumors Many studies ongoing Intravenous CC chemokine receptor CCR4 MOR202 MOR03087 Human monoclonal antibody IgG1 Antineoplastic multiple myeloma phase I 2018 Intravenous CD38 Monalizumab NN8765 IPH2201 Humanized monoclonal antibody IgG4κ Disease modifying Rheumatoid arthritis, antineoplastic gynecologic malignancies, and other cancers phase II 2021 NSCLC phase II 2022 s/p stem cell transplant phase I 2020 CLL phase II 2019 Intravenous Killer cell lectin-like receptor subfamily C member1 (NKG2A, CD159A, CD94) that recognize nonclassical HLA (i.e., HLA-E) Morolimumab Human monoclonal antibody IgG1 ?Diagnostic No studies in pub med, creative lab or FDA substance Rhesus factor Mosunetuzumab RG7828 BTCT4465A Humanized monoclonal antibody IgG1κ bispecific Antineoplastic NHL phase II 2023 DLBCL phase II 2023 Intravenous Subcutaneous CD3E, MS4A1, CD20 Motavizumab MEDI-524 Numax FDA not approved 2010 Older drug just as effective with less side effects Humanized monoclonal antibody IgG1κ Disease modifying Respiratory syncytial virus phase III completed Safety concerns hives and allergic reactions Intramuscular Respiratory syncytial virus glycoprotein F Moxetumomab pasudotox Lumoxiti FDA 2018 Recombinant immunotoxin comprised of a variable fragment (Fv) of a Murine IgG4 anti-CD22 monoclonal antibody genetically Fused to a truncated fragment of Pseudomonas exotoxin A Antineoplastic Hairy cell leukemia Phase I ALL peds Intravenous CD22 Muromonab-CD3 Muromab Aka teplizimab/MGA031 Orthoclone OKT3 FDA 1986 EU 1986 (country specific approval) Humanized monoclonal antibody IgG2aκ Disease modifying Prevention of kidney transplant rejection Many trials GVHD, NASH and T2DM, giant cell myocarditis AbATE Intravenous Oral CD3 Nacolomab tafenatox Murine monoclonal fragment Fab Antineoplastic ?Colorectal cancer No studies in clinical trial or PubMed C242 antigen Namilumab MT203 Human monoclonal antibody IgG1κ Disease modifying Ank spond psoriasis, RA phase II Subcutaneous Colony-stimulating factor 2 (CSF2) Naptumomab estafenatox TTS-CD3 ANYARA ABR-217620 Murine monoclanl antibody fragment Fab Antineoplastic Nonsmall cell lung carcinoma, renal cell carcinoma phase III completed primary endpoint not achieved Intravenous Tumor-associated antigen 5T4 Naratuximab emtansine IMGN529 Chimeric monoclonal antibody IgG1κ Antineoplastic B-Cell lymphoma NHL Intravenous Tetraspanin-26 (CD37) Narnatumab IMC-RON-8 Ron8 Human monoclonal antibody IgG1κ Antineoplastic Solid tumors phase I Intravenous Human cell surface receptor RON (CD 135) macrophage-stimulating 1 receptor Natalizumab Antegran Antegren Tysabri FDA 2004 EU 2006 Humanized monoclonal antibody IgG4κ Disease modifying Relapsing multiple sclerosis, Crohn's disease Intravenous L selectin (CD62L) α4-subunit of α4β1 and α4β7 integrins of leukocytes (except neutrophils) (VLA-4) Navicixizumab OMP 305B83 Humanized/chimeric monoclonal antibody IgG2κ Antineoplastic Phase I study colorectal gyn tumors Intravenous Delta-like 4 (DLL4) Vascular endothelial growth factor A (VEGF-A) Navivumab CT-P27 Human monoclonal antibody IgG1κ Disease modifying Influenza A No studies PubMed Influenza A virus hemagglutinin HA Naxitamab HU3F8 Humanized monoclonal antibody IgG3 Antineoplastic High-risk neuroblastoma and refractory osteomedullary disease study 2023 ?Intravenous c-Met Ganglioside anti-GD2 Nebacumab Humanized monoclonal antibody IgM Withdrawn for safety, Efficacy and commercial reasons Endotoxin Necitumumab IMC-11F8 Portrazza FDA 2015 EU 2016 Human monoclonal antibody IgG1κ Antineoplastic Nonsmall cell lung carcinoma Intravenous EGFR Nemolizumab CIM331 CD14152 Humanized monoclonal antibody IgG2κ Disease modifying Eczema phase I and II Subcutaneous Interleukin-31 receptor A (IL31RA) NEOD001 Birtamimab ELT1-01 HU2A4 Humanized monoclonal antibody IgG1κ Disease modifying Primary systemic amyloidosis lack clinical benefit Intravenous Amyloid A protein/amyloid light chain Nesvacumab REGN910 SAR307746 Human monoclonal antibody IgG1κ Antineoplastic Solid tumors not as beneficial as other agents in breast cancer Disease modifying Macular degeneration Intravenous Angiopoietin 2 Netakimab Chimeric monoclonal antibody Disease modifying Psoriasis PLANETA study (Russia, future EU and China) Interleukin 17A Nimotuzumab Theracim Theraloc Humanized monoclonal antibodyIgG1κ Antineoplastic Squamous cell carcinoma, head and neck cancer, nasopharyngeal cancer, glioma Intravenous EGFR Nirsevimab MEDI8897 Human monoclonal antibody IgG1κ Disease modifying Respiratory syncytial virus phase II 2018 Intramuscular Respiratory syncytial virus fusion protein (RSVFR) Nivolumab Opdivo FDA 2015 EU 2015 Human monoclonal antibody IgG4κ immunoglobulin Antineoplastic agent Programmed death receptor-1 (PD-1) blocking antibody NSCLC, bladder cancer, renal cell cancer phase III 2021 Hodgkin lymphoma Melanoma Small cell lung cancer Squamous carcinoma head and neck Colorectal cancer GBM no added benefit 2017 Intravenous Blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2 Nofetumomab merpentan Verluma FDA 1996 No longer marketed in USA Murine monoclonal fragment IgG2bκ Fab Cancer diagnostic imaging SCLC Antitumor Membrane-spanning 4-domains, subfamily A, member 1 Obiltoxaximab ETI-204 Anthim FDA 2016 Chimeric monoclonal antibody IgG1κ Disease modifying Bacillus anthracis anthrax phase IV 2021 Intravenous Intramuscular Bacillus anthracis spores PA component of B. anthracis toxin Obinutuzumab GA101HUMAB RG7159 RO5072759 Afutuzumab Gazyvaro FDA 2013 Humanized monoclonal antibody IgG1κ Antineoplastic lymphoma phase II (MCL, DLBCL) Chronic lymphocytic leukemia Phase II 2021 Intravenous CD20 Induces B-cell apoptosis Ocaratuzumab LY2469298 AME-133V Humanized monoclonal antibody IgG1κ Antineoplastic NHL Pemphigus phase III Intravenous CD20 Ocrelizumab Ocrevus FDA 2017 Humanized monoclonal antibody IgG1κ Disease modifying Multiple sclerosis Intravenous CD20 Odulimomab Murine monoclonal antibody Disease modifying Transplant rejection Only studied in mice Lymphocyte function-associated antigen-1 (LFA-1 (CD11a)) Ofatumumab Arzerra FDA 2009 EU 2010 Human monoclonal antibody IgG1κ Complement-dependent cytotoxicity (CDC) Antineoplastic CLL Phase III 10% ORR after ritux Phase II as first line 86% ORR With CHOP 100% ORR with 62% CR Intravenous CD20 Olaratumab IMC3G3 Lartruvo FDA 2016 EU 2016 Human monoclonal antibody IgG1κ Antineoplastic Sarcoma phase II 2023 Ovarian not beneficial Intravenous Platelet derived growth factor receptor alpha (PDGF-R α) Oleclumab MEDI9447 Human monoclonal antibody IgG1λ Antineoplastic pancreatic phase II 2021 Colorectal cancer Bladder cancer phase I 2020 Breast cancer phase II 2022 NSCLC phase II 2022 Intravenous? 5′-nucleotidase CD73 Olokizumab Humanized monoclonal antibody IgG4κ Disease modifying rheumatoid arthritis Phase I 2014 phase IIb mod results IL6 Omalizumab IGE25 RG3648 Xolair Humanized monoclonal antibody IgG1κ Disease modifying allergic asthma Urticaria Subcutaneous IgE Fc region Omburtamab Murine monoclonal antibody IgG1κ Antineoplastic Neuroblastoma Phase III 2022 Intracerebroventricular treatment CD276 OMS721 Human monoclonal antibody Disease modifying Atypical hemolytic uremic syndrome phase III 2020 Lupus nephritis phase II 2018 Intravenous Mannan-binding lectin-associated serine protease-2 (MASP-2) Onartuzumab PRO143966 RO5490258 METMAB Humanized monoclonal antibody IgG Antineoplastic Intravenous Human scatter factor receptor kinase Ontuxizumab MORAB-004 Chimeric/humanized monoclonal antibody Antineoplastic No clinical response Intravenous Endosialin tumor endothelial marker-1 (TEM1) Onvatilimab Human monoclonal antibody IgG1κ Nothing in PubMed Vista (V-domain immunoglobulin suppression of T activation (VSIR) Opicinumab BIIB033 Human monoclonal antibody IgG1 Disease modifying multiple sclerosis Phase II 2020 Leucine-rich repeat and immunoglobulin domain containing neurite outgrowth inhibitor receptor interacting protein-1 (LINGO-1) LINGO-1 Oportuzumab monatox VB4-845 Vicinium Proxinium FDA 2005 EU 2005 Additional approval pending 2019 Humanized monoclonal antibody fragment scFv Antineoplastic Bladder phase III Head and neck cancer Intravescical Epithelial cell adhesion molecule (EPCAM) and tumor-associated calcium signal transducer 1 (TACSTD1) and pseudomonas exotoxin A immunotoxin fusion protein (anti-EPCAM antibody fragment-Pseudomonas exotoxin fusion protein) Oregovomab MAB-B43.13 OvaRex Murine monoclonal antibody IgG1κ Antiidiopathic antibody to ovarian antigen CA-125 Antineoplastic Ovarian cancer Not effective in achieving increase RFS or OS Ovarian phase I 2021 Phase II 2019 Subcutaneous Intravenous CA-125 Orticumab RG7418 Human monoclonal antibody fragment Fab Disease modifying Antiinflammatory Oxidized low-density lipoprotein oxLDL Otelixizumab Chimeric humanized monoclonal antibody IgG1 Disease modifying Diabetes mellitus type 1 TTEDD phase II DEFEND-1 phase III failed DEFEND-2 phase III- no real benefit Subcutaneous CD3 Otilimab MOR103 GSK3196165 Human monoclonal antibody IgG1λ Disease modifying Osteoarthritis, rheumatoid arthritis phase II 2012 Multiple sclerosis phase II 2014 Intravenous Granulocyte-macrophage colony-stimulating factor (GMCSF) Otlertuzumab TRU-016 Humanized monoclonal antibody IgG fragment Antineoplastic CLL phase I and II 2014 and 2019 Intravenous CD37 Oxelumab OX40L R4930 HUMAB OX40L Human monoclonal antibody IgG1κ Disease modifying Asthma mainly preclinical mice Many clinical studies ongoing leukemia and asthma Intravenous OX-40 (CD252) Ozanezumab GSK1223249 Humanized IgG1 Disease modifying ALS phase II 2015 ALS no good Intravenous Neurite outgrowth inhibitor (NOGO-A) Ozoralizumab ATN 103 Humanized monoclonal antibody Disease modifying Rheumatoid arthritis phase II 2012 Subcutaneous TNF-α Pagibaximab Chimeric monoclonal antibody Disease modifying Staph sepsis low birth weight infants Phase II/III studies 2010 Intravenous Lipoteichoic acid Palivizumab Synagis, Abbosynagis FDA 1998 EU 1999 Humanized monoclonal antibody IgG1κ Disease modifying RSV many phase III studies Intramuscular F protein of respiratory syncytial virus Pamrevlumab FG-3019 Human monoclonal antibody IgG1κ Disease modifying Idiopathic pulmonary fibrosis (IPF), Antineoplastic Pancreatic cancer Muscular dystrophy phase II 2021 Diabetes nephropathy Connective tissue growth factor (CTGF) Insulin-like growth factor binding protein 8 (IGFBP-8) Panitumumab ABENIX ABX-EGF https://en.wikipedia.org/wiki/List_of_therapeutic_monoclonal_antibodies - cite_note-WHOList91-38 Vectibix FDA 2006 EU 2007 Human monoclonal antibody IgG2κ Antineoplastic Metastatic colorectal cancer Intravenous EGFR/erbB-1/HER1 PankoMab-GEX Gatipotuzumab Humanized monoclonal antibody IgG1κ Antineoplastic Phase IIb 2017 Phase I solid tumors 2019 Intravenous Tumor-specific glycosylation of MUC1 Panobacumab Aerumab 11 AR-101 KBPA-101 Human monoclonal antibody Antimicrobial Pseudomonas aeruginosa infection Intravenous Pseudomonas aeruginosa serotype O11 Parsatuzumab MEGF0444A RG-7414 Human monoclonal antibody IgG1κ Antineoplastic Colorectal cancer phase II 2014 no benefit Epidermal growth factor-like domain 7 (EGFL7) Pascolizumab Humanized monoclonal antibody Disease modifying Not effective trails aborted IL-4 Pasotuxizumab Chimeric/humanized monoclonal antibody fragment Antineoplastic No studies Folate hydrolase/prostate-specific membrane antigen (PSMA) Pateclizumab RG7415 PRO283698 MLTA3698A Humanized monoclonal antibody IgG1κ Disease modifying rheumatoid arthritis Phase II not as efficacious as adalimumab but had response Subcutaneous Lymphotoxin-α Patritumab AMG888 U3-1287 Human monoclonal antibody IgG1κ Antineoplastic May not be beneficial head/neck NSCLC CT site ErbB3 (HER3) Spartalizumab PDR001 FDA review possible 2019 Humanized monoclonal antibody Antineoplastic Breast cancer phase II 2021 NSCLC 2021 Melanoma phase II 2022 Phase III 2020 Intravenous PD1, PDCD1, CD279 Pembrolizumab MK-3475 Keytruda FDA 2014 EU 2015 FDA 2018 for metastatic Merkel cell carcinoma, HCC, NSCLC Humanized monoclonal antibody IgG4κ Antineoplastic Squamous carcinoma trachea, NSCLC , urothelial (HCC phase II) Melanoma cHL, LgB cell lymph Gastric cancer Cervical cancer Hepatocellular carcinoma Intravenous Trials for multiple myeloma discontinued by FDA PD-1 Pemtumomab HMFG1 antibody labeled with 90Yttrium Theragyn Murine monoclonal antibody Antineoplastic Phase III Europe 2009/US 2013 no benefit after 3.5 years follow-up MUC1/human milk fat globule antigen 1 (HMFG1) Perakizumab Humanized monoclonal antibody IgG1κ Disease modifying psoriatic arthritis Phase I discontinued IL 17A Pertuzumab Perjeta FDA2012 EU 2013 Omnitarg Humanized monoclonal antibody IgG1 Antineoplastic agent HER2-positive metastatic breast cancer Gastric/breast cancer Phase III gastric Intravenous Extracellular dimerization domain (subdomain II) of the human epidermal growth factor receptor 2 protein (HER2/neu) Pexelizumab Humanized scFv Disease modifying acute myocardial infarctions APEX-AMI trial negative results PRIMO-CABG I and II trials no significant benefit C5 Pidilizumab CT-011 Humanized monoclonal antibody IgG1κ Antineoplastic Mult myeloma DLBCL Pontine glioma Pancreas Melenaoma HCC Antiinfection Intravenous PD-1 Pinatuzumab vedotin Humanized monoclonal antibody ADC consisting of the microtubule-disrupting agent, monomethyl auristatin E (MMAE), conjugated to an anti-CD22 mAbvia the protease-cleavable peptide linker maleimidocaproylvaline-citrulline(vc)-p-aminobenzoyloxycarbonyl Antineoplastic B-cell NHL phase I study good response Phase II completion 2019 Intravenous CD22 Pintumomab Murine monoclonal antibody Not therapeutic Diagnostic imaging adenocarcinoma antigen Adenocarcinoma (imaging) Placulumab Human monoclonal antibody V-kappa)2 FC Disease modifying pain and inflammatory diseases Development discontinued 2012 Human TNF Plozalizumab MLN1202 HU1D9 Withdrawn by company Humanized monoclonal antibody IgG1κ Disease modifying Diabetic nephropathy and arteriovenous graft patency RA no benefit Intravenous CC chemokine receptor 2 (CCR2) Pogalizumab MOXR0916 R07021608 Vonlerolizumab Humanized monoclonal antibody IgG1κ Antineoplastic Solid tumors phase I 2019 may be safe but may not be effective No formal manuscripts yet Intravenous Tumor necrosis factor receptor superfamily member 4 (ACT35, OX40, CD134) Polatuzumab vedotin FCU2711 RO5541077-000 FDA review 2018 Humanized monoclonal antibody IgG1κ Antineoplastic NHL phase II 2019 DLBCL phase III 2023 Intravenous CD79B Ponezumab RN1219 PF-04360365 Humanized monoclonal antibody IgG2 Disease modifying Alzheimer's disease Safe but no clinical efficacy 2013 Intravenous Human beta-40-amyloid Aβ40 Porgaviximab C2G4 Chimeric monoclonal IgG1κ Antiinfectious Ebola virus disease No known ongoing studies Zaire ebolavirus glycoprotein Prasinezumab PRX002 RG7935 RO7046015 Humanized monoclonal antibody IgG1κ Disease modifying Parkinson's disease Phase II 2021 Intravenous Anti-alpha-synuclein (NACP) Prezalizumab AMG-557 MEDI5872 Humanized monoclonal antibody IgG2 Disease modifying SLE phase II 2018 Sjogren's Subcutaneous B7-related protein inducible T-cell costimulator ligand (ICOSL) Priliximab cMT 412 CEN 000029 Chimeric monoclonal antibody Disease modifying Crohn's disease, multiple sclerosis IN FDA no known studies CD4 Pritoxaximab Chimeric monoclonal antibody IgG1κ Antiinfectious E. coli shiga toxin type-1 Pritumumab Human monoclonal antibody IgG1κ Antineoplastic Brain cancer Phase II studies in Japan, could not find literature reportedly increase survivability 10 fold Vimentin Quilizumab MEMP1972A RG-7449 Anti-M1 Humanized monoclonal antibody IgG1κ Disease modifying Asthma phase II 2014 no great benefit Urticaria phase II 2014 no great benefit Allergic rhinitis Subcutaneous Intravenous M1 prime segment of membrane bound IgE (IGHE) Racotumomab Vaxira Murine monoclonal antibody IgG1κ Antineoplastic Nonsmall cell lung cancer phase III 2016 cimavax better (recombinant EGF injection) 2 more months survival over placebo Neuroblastoma phase II 2020 Intradermal Subcutaneous N-glycolylneuraminic acid gangliosides (NGNA ganglioside) Radretumab F16SIP L19SIP radiolabeled with I 331 Human monoclonal antibody Imaging study PET Antineoplastic Lymphoma brain mets 2012 phae I Stage III NSclC Fibronectin extra domain-B Rafivirumab CR57 Human monoclonal antibody IgG1λ Used in cocktail and with vaccination Antiinfectious Rabies (prophylaxis) No known studies Rabies virus glycoprotein Ralpancizumab RN317 PF-05335810 Humanized monoclonal antibody IgG2κ Disease modifying Dyslipidemia phase I 2017 PCSK9 (proprotein convertase subtilisin/kexin type 9, neural apoptosis-regulated convertase 1, NARC1, NARC-1, proprotein convertase 9, PC9) Ramucirumab LY3009806 IMC-1121B Cyramza FDA 2014 EU 2014 Human monoclonal antibody IgG1κ Antineoplastic Urothelial phase III done Adenocarcinoma stomach and GE junction phase II 2023 Colorectal cancer NSCLC HCC phase III 2017 no additional benefit Intravenous VEGFR2 Ranevetmab NV-01 Veterinary monoclonal antibody IgG1κ canine Disease modifying Osteoarthritis in dogs Nerve growth factor-β (NGF-β) Ranibizumab RBZ RG-3645 RHuFAb Lucentis FDA 2006 EU 2007 Humanized monoclonal fragment IgG1κ Fab Disease modifying Macular degeneration (wet form) post market studies phase II Intravitreal Vascular endothelial growth factor A (VEGF-A) Ravagalimab PR-1629977 ABBV-323 Humanized monoclonal antibody IgG1κ Disease modifying UC phase II 2023 Intravenous Subcutaneous CD40 Ravulizumab ALXN1210 Ultomiris FDA 2019 EU pending Humanized monoclonal antibody IgG2/IgG4κ Disease modifying Paroxysmal nocturnal hemoglobinuria (PNH) Phase III 2021 similar to eculizumab, atypical hemolytic uremic syndrome phase III 2021 Intravenous Complement C5 (C5) Raxibacumab ABthrax FDA 2012 Human monoclonal antibody IgG1λ Antiinfectious Treat inhalation anthrax Intravenous Bacillus anthracis protective antigen Refanezumab GSK249320 Humanized monoclonal antibody IgG1κ Disease modifying recovery of motor function after stroke Phase II completed 2011 no benefit Intravenous Myelin-associated glycoprotein Regavirumab MCA C23 TI-23 Human monoclonal antibody Antiinfectious Cytomegalovirus glycoprotein B ONLY STUDIES IN RATS 1994 Cytomegalovirus infection Relatlimab BMS-986016 Human monoclonal antibody IgG4κ Antineoplastic Melanoma phase II 2022 Colon cancer phase II 2022 Chordoma phase II 2020 Cannot find manuscripts but company website phase II good results Glioblastoma phase I 2020 Intravenous Lymphocyte activation gene 3 (LAG3) CD223 Remtolumab ABT-122 Human monoclonal antibody Disease modifying RA Phase II 2016 no increased benefit over adalimumab Subcutaneous Interleukin 17 alpha, TNF-α Reslizumab DCP 835 Scheme 55700 CEP-38072 Cinqair FDA 2016 EU 2016 Humanized monoclonal antibody IgG4κ Disease modifying Inflammations of the airways asthma completed and ongoing, skin and gastrointestinal tract, polyarteritis stage II 2018 Rhino sinusitis 2020 Intravenous Subcutaneous IL-5 Rilotumumab AMG-102 Human monoclonal antibody IgG2κ Antineoplastic Gastric completed phase III 2015 not effective NSCLC phase II 2014 no benefit Glioma phase II no response Intravenous Hepatocyte growth factor (HGF) Rinucumab REGN2176 Human monoclonal antibody IgG4κ Disease modifying neovascular age-related macular degeneration phase II 2014 Intravitreal Platelet-derived growth factor receptor beta Risankizumab ABBV-066 BI-655066 FDA/EU pending approval Humanized monoclonal antibody IgG1κ Disease modifying Crohn's disease phase II good, phase III ongoing psoriasis phase II response better than ustekinumab, psoriatic arthritis, and asthma Subcutaneous IL23A Rituximab GP2013 IDEC-102 RG-105 MabThera, Rituxan FDA 1997 EU 1998 Chimeric monoclonal antibody IgG1κ Antineoplastic Non-Hodgkin lymphomas, chronic lymphocytic leukemias, some autoimmune disorders, i.e., rheumatoid arthritis, >2K studies ongoing Subcutaneous CD20 Rivabazumab pegol Humanized monoclonal antibody fragment Fab’ IgG1κ Antiinfectious No studies found Pseudomonas aeruginosa type III secretion system Rmab Rabishield Made in India Human monoclonal antibody Antiinfectious Postexposure prophylaxis of rabies Rabies virus G glycoprotein Robatumumab 19D12 SCH 717454 MK-7454 P04722 Human monoclonal antibody IgG1κ Antineoplastic Colorectal phase II 2009 little benefit Ewings no response 2016 Intravenous Insulin-like growth factor I (IGF-1 receptor) (CD221) Roledumab Human monoclonal antibody IgG1κ Immunomodulation Rh disease Phase III 2017 Intravenous RHD Romilkimab SAR156597 HUBTI3_2_1 Humanized chimeric monoclonal antibody IgG4 bispecific Disease modifying Systemic sclerosis phase II 2019 Pulm fibrosis phase II 2017 no benefit Subcutaneous Interleukin 13 and IL4 Romosozumab Evenity FDA pending EU pending Japan 2018 Humanized monoclonal antibody IgG2κ Disease modifying Postmenopausal osteoporosis phase III study FRAME Men phase III BRIDGE phase III Intravenous Sclerostin/scleroscin SOST Rontalizumab rhuMAb IFNalpha Humanized monoclonal antibody Disease modifying Systemic lupus erythematosus phase II 2013 end points not met Subcutaneous IFN-α Rosmantuzumab OMP-131R10 Humanized monoclonal antibody IgG1κ Antineoplastic Colorectal cancer phase I 2018 Intravenous Root plate-specific spondin r-spondin-3 WNT? (wingless/integrated) Rovalpituzumab tesirine SC0002 SC16LD6.5 ABBV-181 Humanized monoclonal antibody IgG1κ Antineoplastic Small cell lung cancer phase I 2018 Phase II 2024 Intravenous Delta-like ligand-3 (DLL3) Rovelizumab Hu23F2G LeukArrest Humanized monoclonal antibody IgG1κ Disease modifying Hemorrhagic shock, MI stroke phase III goals not met 2000 CD11, CD18 Rozanolixizumab UCB7665 Chimeric/humanized monoclonal antibody IgG4κ Thrombocytopenia ITP phase II 2019 Myasthenia gravis phase II 2018 Subcutaneous Intravenous Neonatal Fc receptor (FCGRT) Ruplizumab Antova Humanized monoclonal antibody Disease modifying lupus and lupus nephritis not effective Life-threatening thromboembolism BioDrugs. 2004; 18(2):95–102. Costimulation blockade in the treatment of rheumatic diseases CD154 (CD40L) Sacituzumab govitecan IMMU-132 FDA/EU pending approval Humanized monoclonal antibody IgG1κ Antineoplastic agent Prostate cancer phase II 2021 Urothelial phase II 2020 Trip neg breast ca phase III 2020 NSCLC SCLC UC Intravenous Tumor-associated calcium signal transducer 2 (TROP-2) inhibits topoisomerase I Samalizumab ALXN6000 BAML-16-001-S1 Humanized monoclonal antibody IgG2/G4κ Antineoplastic CLL MM phase I 2010 (terminated by sponsor) AML phase II 2021 Intravenous OX-2 membrane glycoprotein (CD200) Samrotamab vedotin Chimeric/humanized monoclonal antibody IgG1κ Antineoplastic No studies found Leucine-rich repeat-containing protein 15 (LRRC15) Sarilumab REGN88 SAR153191 Kevzara FDA?EU/Japan under review approved in Canada Human monoclonal antibody IgG1κ Disease modifying rheumatoid arthritis phase III 2015/2020/2027(preg exposure), ankylosing spondylitis Juvenile idiopathic arthritis phase II 2022 Subcutaneous IL6 Satralizumab SA237 Sapelizumab FDA review possible 2019 Humanized monoclonal antibody IgG2κ Disease modifying Neuromyelitis optica phase III 2019/2020 Subcutaneous? IL6 receptor Satumomab pendetide OncoScint CR103 FDA 1992 Murine monoclonal antibody IgGκ fragment Fab’ Diagnostic imaging Detection colorectal and ovarian cancer Intravenous Tumor-associated glycoprotein (TAG-72) Secukinumab AIN457 Cosentyx FDA 2015 EU 2015 Human monoclonal antibody IgG1κ Disease modifying Uveitis, rheumatoid arthritis psoriasis phase II 2019 over 100 other studies arthritis ; psoriatic psoriasis; spondylitis; ankylosing Subcutaneous IL 17A Selicrelumab CP 870.893 RG7876 RO-7009789 Human monoclonal antibody IgG2κ Antineoplastic Solid tumors phase I 2020 Pancreatic cancer phase II 2020 Colon cancer phase II 2021 Mesothelioma phase ib 2015 Subcutaneous Intravenous Tumor necrosis factor receptor superfamily member 5 (CD40) Seribantumab MM121 SAR256212 Human monoclonal antibody IgG2λ Antineoplastic Breast phase II 2020 Ovarian phase I 2014 Intravenous Receptor tyrosine-protein kinase erbB-3 (HER3) Setoxaximab Chimeric monoclonal antibody IgG1κ Antiinfection E. coli No known studies or clinical use E. coli shiga toxin type-2 Setrusumab BPS804 MOR05813 Human monoclonal antibody IgG2 Disease modifying Osteogenesis imperfecta phase II 2020 Intravenous Sclerostin (SOST) Sevirumab MSL-109 Antiinfectious CMV retinitis early termination trial secondary to safety Phase II 2003 Cytomegalovirus infection SHP647 Ontamalimab PF-00547659 Human monoclonalantibodyIgG2κ Disease modifying Crohn's/UC phase III 2020–2025 × 7 Phase II study 2007 better response in UC than in Crohn (?more time needed to evaluate clinical significance Subcutaneous Mucosal addressin cell adhesion molecule (MADCAM) Sibrotuzumab BIBH1 F19 Humanized monoclonal antibody IgG1κ Antineoplastic Colorectal cancer phase II 2003 failed Lung cancer2001 Intravenous FAP Sifalimumab MDX-1103 MEDI-545 CP145 Humanized monoclonal antibody IgG1κ Disease modifying SLE phase II 2015 dermatomyositis, polymyositis Intravenous Subcutaneous IFN-α Siltuximab CLLB8 CNTO-328 Sylvant FDA 2014 EU 2014 Chimeric monoclonal antibody IgG1κ Antineoplastic Multiple myeloma phase II 2019 DM type I phase I 2017 Schizophrenia adjunct 2020 phase II Multicentric Castleman's disease (MCD) with HIV negative and HHV-8 negative Intravenous IL-6 Simtuzumab AB0024 GS-6624 Humanized monoclonal antibody IgG4κ Disease modifying Hepatic fibrosis Phase II 2016 no benefit Pulm fibroses phase II 2017 no benefit Myelo fibr 2017 phase II Subcutaneous Intravenous Lysyl oxidase homolog 2 (LOXL2) Siplizumab MEDI-507 Humanized monoclonal antibody IgG1κ Antineoplastic CD2 T Or NK cells Sirtratumab vedotin Human monoclonal antibody Antineoplastic Nothing in PubMed or clinical trials SLITRK6 Sirukumab Human monoclonal antibody IgG1κ Disease modifying Rheumatoid arthritis Phase III done good results Subcutaneous IL-6 Sofituzumab vedotin Humanized monoclonal antibody Antineoplastic Ovarian pancreatic Phase I (2014) CA-125 Solanezumab LY2062430 Humanized monoclonal antibody IgG1 Disease modifying Alzheimer's Phase III study discontinued no effect In preclinical trial for secondary prevention 2022 Hereditary AD phase III 2021 Intravenous Beta amyloid Solitomab MT110-011 AMG110 Murine monoclonal antibody bispecific T-cell engager (BiTE) Antineoplastic Gastrointestinal, lung, and other cancers Phase I 2015 Intravenous Epithelial cell adhesion molecule (EpCAM) CD3 Sonepcizumab LT1009 iSONEP Humanized monoclonal antibody Disease modifying Choroidal and retinal neovascularization phase II 2015 not so good Antineoplastic phase II renal cancer 2017 potential Intravenous Intravitreous Sphingosine-1-phosphate (S1P) Stamulumab Humanized monoclonal antibody Disease modifying muscular dystrophy Animal studies, minimal efficacy Phase I/II studies ongoing (no improvement) Intravenous Myostatin Sulesomab IMMU-MN3 LeukoScan EU 1997 Murine monoclonal IgG1 fragment Fab′ Diagnostic Osteomyelitis (imaging) NCA-90 (granulocyte antigen) Suptavumab REGN2222 SAR438584 Human monoclonal antibody IgG1κ Antiinfectious Medically attended lower respiratory disease phase III 2017 not meet primary endpoint Another study no data yet at 30 mg/kg dose Intramuscular Resp sync virus fusion protein (RSVFR) Sutimlimab BIVV009 Chimeric/humanized monoclonal antibody IgG4κ Disease modifying cold agglutinin disease phase III 2020 Intravenous Complement C1s (C1s) Suvizumab KD-247 Humanized monoclonal antibody IgG1κ Antiinfectious HIV Phase I KD-247 2007 Intravenous Human immunodeficiency virus glycoprotein 120 third variable loop Suvratoxumab MEDI4893 Human monoclonal antibody IgG1κ Disease modifying Nosocomial pneumonia phase II 2018 Intravenous Staphylococcus aureus alpha toxin Tabalumab LY2127399 Human monoclonal lantibodyIgG4κ Antineoplastic Rheum arthr phase III 2013 no signif response SLE phase III 2015 endpoints not met Mult myelo phase I 2014 may not treat but be prognostic Subcutaneous Cytokine B-cell activating factor (BAFF) Tacatuzumab tetraxetan HAFP-31 AFP-Cide Humanized monoclonal antibody yttrium 77 Antineoplastic No studies in clinical trial or PubMed Alpha-fetoprotein Tadocizumab C4G1 YM337 Humanized monoclonal antibody fragment IgG1κ Fab’ Disease modifying Percutaneous coronary intervention phase I 1999 ?not further developed Integrin αIIbβ3 Talacotuzumab CSL362 JNJ-56022473 Humanized monoclonal antibody IgG1-2κ Antineoplastic AML phase III 2018 MDS phase II 2019 SLE 2019 phase I Intravenous Interleukin 3 receptor subunit-α (IL3Rα, CD123) Talizumab C21/AL-90 TNX-901 Humanized monoclonal antibody IgG1κ Disease modifying Peanut allergy Allergic reaction Phase II 2003 good results legal issues shelved the drug Subcutaneous IgE Tamtuvetmab AT-005 Tactress Canine monoclonal antibody IgG2λ CD52 Tanezumab RN624 PF-4383119 FDA review possible 2019 Humanized monoclonal antibody IgG2 Disease modifying Pain Osteoarthritis Back pain Metastatic cancer pain Phase II ∼2008 Nerve growth factor (NGF) Tanibirumab Olinvacimab TTAC-0001 Human monoclonal antibody IgG1 Disease modifying Antineoplastic Phase I glioblastoma 2020 Breast cancer phase I 2020 AMD murine no human studies found Intravenous VEFR-2 Taplitumomab paptox Murine monoclonal antibody IgG1κ Antineoplastic No studies pub med or clinical trials CD19 Tarextumab OMP-59R5 Human monoclonal antibody IgG2 Antineoplastic Phase II trial NSCLC no benefit 2017 Pancreatic phase II 2017 Intravenous Notch2/3, Notch receptor Tavolimab MEDI0562 Chimeric/humanized monoclonal antibody IgG1κ Antineoplastic Head and neck phase I 2024 Ovarian cancer phase II 2023 Tumor necrosis factor receptor superfamily member 4 (TNFRS4) OX40L receptor (CD134) Technetium (99 mTc) acritumomab Rabbit monoclonal IgG Not for use in humans- research purpose only CEA Technicium (99 mTc) Fanolesomab NeutroSpec FDA2004 Murine monoclonal IgM radiolabeled Disease modifying osteomyelitis Sales and marketing suspended (2005) Diagnostic scans for acute appendicitis Intravenous CD15 Tefibazumab INH–H2002 Aurexis Humanized monoclonal antibody IgG1κ Antiinfectious Staphylococcus aureus infection Phase II 2006 Intravenous Clumping factor A Telimomab aritox (TAB-885) Recombinant murine monoclonal antibody Fab with ricin Antineoplastic T Cell lymphoma/leukemia No studies in pub med or clinical trials CD5 Telisotuzumab vedotin ABT-700 Humanized monoclonal antibody IgG1κ Antineoplastic Phase I 2017 SCLC phase II 2022 NSCLC phase II 2021 Intravenous Hepatocyte growth factor receptor HGFR Tenatumomab Murine monoclonal antibody IgG2b Antineoplastic Phase I 2017 Phase II brain tumors 2010 Intravenous P24821 , tenascin C Teneliximab Chimeric monoclonal antibody IgG1 Not in clinical trials 2009 CD40 (TNF receptor superfamily member 5) Teplizumab MGA031 PRV-031 hOKT3g1(Ala-Ala) Humanized monoclonal antibody IgG1κ Disease modifying type I DM phase II completion AbATE trial 2019 Psoriasis phase I and II completed 2010 study stopped secondary to injection reaction severe allergy Intravenous Subcutaneous CD3 Tepoditamab Human monoclonal antibody IgG1κ bispecific Antineoplastic No studies on PubMed or clinical trials c-type dendritic cell-associated lectin 2 (CLEC-2A, MCLA-117) and CD3 Teprotumumab RV001 R-1507 RO4858696 HZN-001 FDA review possible 2019 Human monoclonal antibody Disease modifying Thyroid eye disease phase II 2017 Graves phase III 2020 Intravenous Insulin-like growth factor receptor type I (IGF-1 receptor) (CD221) Tesidolumab LFG316 NOV-4 Human monoclonal antibody Phase I 2017 PNH phase II 2020 AMD phase II 2015 not beneficial Intravenous Intravitreous C5 Tetulomab tetraxetan LU-177 Betalutin Humanized monoclonal antibody Antineoplastic Animal studies 2013 CD37 Tezepelumab MEDI9929 AMG-157 Human monoclonal antibody IgG2λ Disease modifying Asthma, atopic dermatitis Phase II 2017 Subcutaneous Thymic stromal lymphopoietin (TSLP) Theralizumab TGN1412 TAB08 Humanized monoclonal antibody Antineoplastic Solid tumors phase I 2020 Disease modifying Rheum arth, SLE phase II Intravenous CD28 History of cytokine storm at higher doses 2006 Tibulizumab LY3090106 Humanized monoclonal antibody bispecific tetravalent Disease modifying Autoimmune disorder Phase I 2020 Subcutaneous Intravenous No manuscripts found specific to this antibody Human B-cell activating factor of the tumor necrosis factor family interleukin 17 (BAFF) Tigatuzumab CS-1008 TRA-8 Humanized monoclonal antibody IgG1κ Antineoplastic Colon phase II 2011no added benefit Colon phase I 2013 NSCLC phase II 2011 no benefit Pancreatic phase II 2008 benefit TN breast canc 2015 phase II no added benefit Cytokine receptor DR5 (death receptor 5) TRAIL-R2 Tildrakizumab MK-3222 SCH-900222 Ilumya Ilumetri FDA 2018 Humanized monoclonal antibody IgG1κ Immunologically mediated inflammatory disorders Mod/severe psoriasis phase III 2018-20 Subcutaneous IL23 Timigutuzumab Humanized monoclonal antibody IgG1κ Antineoplastic No studies in clinical trial or PubMed erbB2/HER2 Timolumab BTT-1023 Human monoclonal antibody Disease modifying Scler cholang phase II 2019 Intravenous AOC3 Tiragotumab MTIG-7192A RG6058 RO7092284 Human monoclonal antibody IgG1κ Antineoplastic Phase I 2020 NSCLC phase II 2021 HL phase II 2019 Intravenous Nothing published yet T-cell IG and immune-receptor tyrosine-based inhibitory motif (TIGIT) Tislelizumab China pending approval Humanized monoclonal antibody Antineoplastic NSCLC phase III 2020 Gastric phase III 2022 Esophageal cancer phase III 2021 NHL phase II 2020 Intravenous Nothing published yet 2019 PCDC1, CD279 Tisotumab vedotin Human monoclonal antibody IgG1κ Antineoplastic Ovary cancer Cervix cancer Endometrium cancer Bladder cancer Prostate cancer Esophagus cancer Lung cancer, NSCLC Squamous cell carcinoma of the head and neck Pancreatic phase II 2022/3 Intravenous Coagulation factor III Tocilizumab MRA R-1569 RG-1569 RHPM-1 RO-4877533 Atlizumab Actemra, RoActemra FDA 2010 EU 2009 Humanized monoclonal antibody IgG1κ Disease modifying rheumatoid arthritis >100 studies Behcet syndrome Intravenous Subcutaneous IL-6 receptor Tomuzotuximabfibri Humanized monoclonal antibody IgG1κ Antineoplastic Phase I 2019 EGFR, HER1 Toralizumab E−6040 IDEC-131 Humanized monoclonal antibody IgG1κ Disease modifying rheumatoid arthritis, lupus nephritis etc. Phase II trials failed with TE CD154 (CD40L) Tosatoxumab Human monoclonal antibody IgG1λ Antiinfectious No studies PubMed or Clin trials Staphylococcus aureus α-hemolysin Tositumomab and iodine 131 Tositumomab Bexxar FDA 2003 Murine monoclonal antibody IgG2aλ Antineoplastic Follicular lymphoma ( NHL ) >100 studies Intravenous CD20 Tovetumab MEDI-575 Human monoclonal antibody IgG2κ Antineoplastic Phase I/II 2012 Glioblastoma limited clin activity Intravenous Platelet-derived growth factor receptor α (CD140a) Tralokinumab CAT-354 Human monoclonal antibody IgG4 Disease modifying asthma phase IIb +/−, atopic dermatitis phase II 2016 Intravenous Subcutaneous IL-13 Trastuzumab 4D5v8 R-597 SYD977 Herceptin FDA 1998 EU 2000 Herceptin Hylecta FDA 2019 –trastuzumab/hyaluronidase Herzuma 2018 Humanized monoclonal antibody IgG1κ Antineoplastic Breast cancer Gastric and gastro-esophageal junction cancer HER2-positive phase III Subcutaneous Intravenous HER2/neu Trastuzumab Deruxtecan DS-8201 Hercion FDA breakthrough therapy Antibody drug conjugate humanized antibody IgG1κ with topoisomerase I inhibitor (DXd) Antineoplastic breast cancer phase I study breast, gastric, colorectal, salivary, and nonsmall cell lung cancer participated in part 2 2020 phase II DESTINY-Breast01 HER2 Trastuzumab emtansine RG-3502 PRO132365 Kadcyla FDA2013 EU 2013 Humanized monoclonal antibody IgG1κ as ADC Antineoplastic Breast cancer Intravenous HER2/neu TRBS07 Ektomab 3funct Antineoplastic Melanoma GD2 ganglioside Tribbles-related protein (TRB) family members are the mammalian orthologs of Drosophila tribbles. Tribbles was originally identified as a cell cycle regulator during Drosophila development. Tribbles genes are evolutionary conserved, and three TRB genes (TRB1, TRB2 and TRB3) have been identified in mammals. TRBs are considered pseudokinases because they lack an ATP binding site or one of the conserved catalytic motifs essential for kinase activity. Instead, TRBs play important roles in various cellular processes as scaffolds or adaptors to promote the degradation of target proteins and to regulate several key signaling pathways. Recent research has focused on the role of TRBs in tumorigenesis and neoplastic progression. In this review, we focus on the physiological roles of TRB family members in tumorigenesis through the regulation of the ubiquitin-proteasome system and discuss TRBs as biomarkers or potential therapeutic targets in cancer Tregalizumab BT-061 Humanized monoclonal antibody IgG1κ Disease modifying Rheumatoid arthritis Phase IIb no benefit Subcutaneous CD4 Tremelimumab (aka ticilimumab) ∗CP-675,206 Human monoclonal antibody IgG2 Antineoplastic agent NSCLC, small cell lung cancer, urethelial cancer phase II 2020, head and neck cancer and colon phase I 2021 Mesothelial phase IIb DETERMINE not beneficial >100 studies CTLA4 (cytotoxic T lymphocyte-associated antigen 4, CD152 Trevogrumab REGN1033 SAR391786 Human monoclonal antibody IgG4κ Disease modifying Muscle atrophy due to orthopedic disuse and sarcopenia phase II 2020 Myostatin, growth differentiation factor 8 (GDF8) TRL3d3 3D3 IgG Studies only in mice to this point Ati-G protein antibody (RSVGV) Tucotuzumab celmoleukin EMD-273066 HUKS-IL2 Humanized monoclonal antibody IgG1 Antineoplastic Ovarian phase II 2008 Lung, kidney, bladder phase I 2000 no benefit Intravenous Interleukin2 (EpCAM) Tuvirumab Humanized monoclonal antibody Antiinfectious Not effective in achieving primary efficacy as assessed by neutralization of circulating HBsAg Intravenous Hepatitis B virus surface antigen Ublituximab TG-1101 FDA review pending 2019 Chimeric monoclonal antibodyIgG1κ Antineoplastic Chronic lymphocytic leukemia, follicular cell lymphoma phase II 2020 Disease modifying Multiple sclerosis phase II 2019, phase III 2021 Awaiting result looks good prelim Intravenous CD20 MS4A1 Ulocuplumab Human monoclonal antibody IgG4 Antineoplastic CLL phase I 2014 Phase I/II Waldenstrom macroglobulinemia 2025 Phase I/II AML 2021 Intravenous CXCR4 (CD184) Urelumab BMS-663513 Human monoclonal antibody IgG4κ Antineoplastic CLL phase II 2020 Solid tumors phase II 2023 Intravenous Human receptor 4-1BB (CD137) Urtoxazumab TMA-15 Humanized monoclonal antibody IgG1κ Disease modifying EHEC animal studies Escherichia coli (EHEC) shiga toxin 2 Ustekinumab Stelara FDA 2009 EU 2009 Human monoclonal antibody IgG1κ Disease modifying Crohn disease Plaque psoriasis Psoriatic arthritis Subcutaneous Intravenous p40 subunit of interleukin 12 (IL-12p40), IL-23 Utomilumab PF-05082566 Human monoclonal antibody IgG2 Antineoplastic Diffuse large B-cell lymphoma Phase I 2021 phase II 2020 Breast phase II 2025 Intravenous 4-1BB (CD137) Vadastuximab talirine H2H12EC Chimeric monoclonal antibody IgG1κ Antineoplastic Acute myeloid leukemia phase II 2017 phase III 2017 MDS phase II 2017 Intravenous CD33 Vanalimab Mitazalimab Humanized monoclonal antibody IgG1λ Antineoplastic? No studies clinical trial or PubMed Immune checkpoint receptor, tumor necrosis receptor family CD40, (TNFRSF5) Vandortuzumab vedotin Humanized monoclonal antibody Antineoplastic Prostate cancer STEAP1 Vantictumab OMP-18R5 Human monoclonal antibody IgG2mab Antineoplastic NSCLC, breast phase I 2017 Intravenous Frizzled receptor Vanucizumab RG-7221 RO5520985 Humanized monoclonal antibody IgG1κ bispecific ANG-2/VEGF-Amab Antineoplastic Phase I 2018 Intravenous Angiopoietin 2/vascular endothelial growth factor A Vapaliximab BTT-1002 HUVAP Chimeric monoclonal antibody IgG2κ No studies in PubMed or clinical trials Vascular adhesion protein AOC3 (VAP-1) Varisacumab GNR-011 R-84 Human monoclonal antibody IgG1κ No studies in PubMed or clinical trials VEGF-A Varlilumab CDX-1127 Human monoclonal antibody IgG1κ Antineoplastic Solid tumors and hematologic malignancies Phase I 2017, phase II 2019/20 Melanoma phase II 2018/21 Intravenous CD27 Vatelizumab GBR500 SAR339658 Humanized monoclonal antibody IgG4 Disease modifying UC phase II 2016 MS phase II 2016 withdrawn lack of efficacy Α2β1 integrin I domain ITGA2 (CD49b) Vedolizumab LDP02 MLN02 Entyvio FDA 2014 EU 2014 Humanized monoclonal antibody IgG1κ Disease modifying Crohn disease Ulcerative colitis In CD resolution extraintestinal manifestations Intravenous Integrin α4β7 Selectively blocks trafficking of Memory T cells to inflamed gut tissue by inhibiting a4b7-mucosal addressin cell adhesion molecule-1 (MAd-CAM-1) interaction Veltuzumab IMMU-106 HA20 Humanized monoclonal antibody IgG1κ Antineoplastic Non-Hodgkin's lymphoma phase II 2013 ITP phase II 2016 Subcutaneous CD20 Vepalimomab Murine monoclonal antibody AOC3 (vascular adhesion protein-1) Vesencumab MNRP1685A Human monoclonal antibody IgG1mab Antineoplastic Solid malignancies Phase I 2011 proteinuria Neuropilin1 (NRP1) Visilizumab Nuvion Humanized monoclonal antibody IgG2 Disease modifying Prevent GVHD Not effective in UC CD3 Vobarilizumab Humanize monoclonal scFv Disease modifying inflammatory autoimmune diseases Nothing in PubMed IL6R Volociximab M200 Chimeric monoclonal antibody IgG4κ Antineoplastic Solid tumors NSCLC phase I/II 2010 Disease modifying phase I AMD terminated no results Integrin α5β1 Vopratelimab JTX-2011 Humanized monoclonal antibody IgG1κ Antineoplastic Solid tumors phase II 2022 Intravenous Inducible T-cell costimulator (ICOS) Vorsetuzumab mafodotin H1F6 SGN-70 Humanized monoclonal antibody Antineoplastic Phase I 2017 Intravenous CD70 Votumumab HumaSPECT Diagnostic EU 1998 Withdrawn from market 2003 Human monoclonal antibody Diagnostic Human colon cancer imaging Tumor antigen Cytokeratin tumor-associated antigen (CTAA16.88) Vunakizumab SHR-1314 Humanized monoclonal antibody IgG1 Disease modifying Psoriasis phase II 2019 Subcutaneous Nothing published Interleukin 17 alpha Xentuzumab BI-836845 Humanized monoclonal antibody Antineoplastic Breast, prostate, solid phase I 2019 Intravenous No clinical studies published Insulin-like growth factor (IGF1, IGF2) XMAB-5574 Tafasitamab MOR00208 FDA review possible 2019 Humanized monoclonal immunoglobulin fragment κ Fc Antineoplastic Diffuse large B-cell lymphoma phase II 2015/18/19/22 phase III 2022 Intravenous CD19 Zalutumumab 2F8 HUMAX-EGFR HuMax-EGFr Suspended for commercialization Human monoclonal antibody Antineoplastic Squamous cell carcinoma of the head and neck phase II 2011 phase III 2016 Intravenous EGFR Zanolimumab HuMax-CD4 (trade name) Humanized monoclonal antibody IgG1κ Antineoplastic CTCL Phase II good results Phase III suspended by company? Intravenous CD4 Zenocutuzumab Humanized monoclonal antibodyIgG1 bispecific epidermal growth factor receptors her2,her3 Antineoplastic ERBB3, HER3 Ziralimumab Human monoclonal antibody IgM Disease modifying immunosuppressive No studies clinical trials or PubMed CD147 (basigin) Zolbetuximab IMAB362 Claudiximab Chimeric monoclonal antibody IgG1κ ADCC enhance antibody Antineoplastic gastric cancer phase I, IIb Phase III 2023 Gastrointestinal adenocarcinomas and pancreatic tumor Intravenous Claudin protein (CLDN18.2) Zolimomab aritox H65-RTA ZX-CD5 Orthozyme CD 5 plus Human monoclonal antibody IgG1 Disease modifying Not effective in preventing GVHD 1994 CD5 Auristatins are water-soluble dolastatin analogs of dolastatin 10. Dolastatin 10 belongs to dolastatin family and it can powerfully bind to tubulin, thus inhibiting polymerization mediated through the binding to the vinca alkaloid-binding domain, and causes cell to accumulate in metaphase arrest.

Ulcerative Colitis

Mabs being studied for UC but not yet approved by the FDA include bimekizumab, etrolizumab, golimumab, mirikizumab, ravagalimab, sacituzumab govitecan, ontamalimab, and vatelizumab. Refer to Table 16.1 .

Autoimmune Diseases

Autoimmune diseases affect many organs and tissues including liver, gall bladder, pancreas (β islet cells in diabetes mellitus), nerve junctions (myasthenia gravis), thyroid, bone and joints, blood vessels, and multiorgan systems, systemic lupus erythematosus (SLE). Autoimmune arthritis is of multiple types including psoriatic, sclerosis, rheumatoid arthritis (RA), and SLE. Many of these diseases are mediated by antibody or cellular autoimmunity but ultimately appear to be secondary to an underlying abnormality in T-cell immune-regulatory control. These disease processes are historically controlled with antiinflammatory agents, immunosuppressive/immunomodulatory agents, or low-dose chemotherapy. Those with resultant hormone deficiencies are supplemented with hormones depleted by the disease process. It is hoped that passive antibody therapy will mitigate the sequelae of these inflammatory processes.

Plaque psoriasis/psoriatic arthritis

Psoriasis affects 2%–3% of the world population and is an inflammatory skin disease. Brodalumab (Siliz) is a human Mab (IgG2κ) with specificity to IL-17 receptor A (IL-17RA). It is FDA approved for treatment of plaque psoriasis, and its mechanism of action is by inhibiting IL-17A, IL-17F, IL-17C, IL-25, and IL-17A/F heterodimer cytokine-induced responses including release of proinflammatory cytokines. When compared to ustekinumab, response rates nearly doubled with brodalumab in phase II and phase III trials during induction and maintenance therapies. 275 , 276

Other therapies currently also approved or being studied for treatment of this disease include bermekimab (MABp1,T2-18C3, CA-18C3, Xilonix), bimekizumab, briakinumab, certolizumab pegol (Cimzia), etanercept (Enbrel), infliximab (Remicade, Inflectra, Remsima), itolizumab (Alzumab), adalimumab (Humira, Amjevita), ustekinumab (Stelara), secukinumab (AIN457, Cosentyx), guselkumab (Tremfya), tildrakizumab (MK-3222, SCH-900,222, Ilumya, Ilumetri), risankizumab (ABBV-066, BI-655,066), mirikizumab (LY3074828), namilumab (MT203), netakimab, and vunakizumab. Refer to Table 16.1 .

Withdrawn from market or ineffective for treating psoriasis include efalizumab (Raptiva), fezakinumab, bleselumab, and teplizumab (MGA031, PRV-031, hOKT3g1(Ala-Ala)) Refer to Table 16.1 .

Systemic juvenile idiopathic arthritis

Abatacept (Orencia) is a recombinant soluble fusion protein of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human IgG1. Its mechanism of action is as selective costimulation modulator as it inhibits T lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. This medication is FDA approved for both juvenile idiopathic arthritis (JIA) and adult RA. 277 , 278 , 279

Rheumatoid Arthritis

Certolizumab pegol alone or with methotrexate improves quality of life in RA and may cause disease remission and reduce joint damage. 280

Ankylosing Spondylitis

Certolizumab pegolis is also approved for use with ankylosing spondylitis.

Systemic Lupus Erythematosus

Belimumab (Benlysta) is a human Mab (IgG1λ) that binds to B-cell activating factor and acts as a B-lymphocyte stimulator-specific inhibitor. It was approved by the FDA in 2011 for treatment of adult patients with active, autoantibody-positive SLE receiving standard therapy. This medication also decreases episodic frequency of lupus nephritis. 281 , 282 , 283

Cardiovascular Disease

Despite marked improvement in survival from cardiovascular disease, this illness remains the number one cause of mortality in the US. This process causes injury to the endothelium of blood vessels of the heart secondary to toxins, accumulation of cholesterol, or chronic low-grade inflammation. Treatment has been preventive, primarily during actual injury or following injury. Therapies involve changes in behavior (diet, exercise, and cessation of tobacco use), pharmacologic to control contributing underlying illness (hypercholesterolemia, hypertension, diabetes type I and II), to diminish injury through thrombolytics, stents, vasodilators, supplemental oxygen, or to control sequelae of infarctions (cardiac dysfunction/failure). Passive antibody therapies are being tried to decrease the effects of some of the contributing factors of atherosclerotic plaque formation.

Abciximab (ReoPro) is a chimeric recombinant monoclonal fragment (IgG1 Fab’) with specificity to platelet glycoprotein IIb/IIIa receptor (CD41 7E3)/Intergrin α-IIb that prevents platelets from binding to fibrinogen. This Mab also prevents coagulation factor XIII from binding to platelets allowing stabilization of clots and are more easily lysed. The Fc portion of the antibody is removed to decrease thrombocytopenias. This antibody is used during high-risk coronary intervention to prevent clot formation and cardiac ischemia. 284

Alirocumab (Praluent) is a human Mab (IgG1) with specificity to proprotein convertase subtilisin/kexin type 9. This medication is used to control cholesterol levels in patients at high risk for cardiovascular events and in patients with familial hypercholesterolemia who are not controlled by other agents. 285 , 286 , 287

Evolocumab (Repatha) is a human Mab (IgG2λ) FDA approved for the treatment of hypercholesterolemia in patients with familial hypercholesterolemia or history of cardiovascular disease. This Mab has specificity to PCSK9. This medication reduced low-density lipoprotein (LDL) and cholesterol levels by 60% even after statin therapy. Hazard ratios for primary and secondary endpoints were less than one (∼0.80–0.85) with fewer cardiovascular-related death or infarction and stroke. 288 , 289

Under future watch is frovocimab (LY3015014) a humanized Mab (IgG4κ) with specificity to PCSK9 that completed phase I and II trials. There was up to 50% reduction in LDL cholesterol levels. Phase III studies have yet to be performed. 290

An additional antibody is lodelcizumab a humanized Mab (IgG1κ); however, no studies were found in clinicaltrials.gov or in Pubmed searches.

Bococizumab is a humanized Mab (IgG2κ) that was in phase III trial, which was discontinued secondary to primary endpoints not being achieved. 291

Neurologic Diseases

Besides autoimmune and malignant diseases of the neurologic system, there are also diseases of the central nervous system classified as degenerative. Such diseases include supranuclear palsy (SNP), Alzheimer's, and Parkinson's. Alzheimer's is likely the most common cause of dementia first described in 1907. This disease may be depicted as presenile or senile dementia and progresses at a similar rate no matter age of onset. This disease has a genetic predisposition causing it to occur in younger age groups. Histological changes include diffuse plaques (containing amyloid), neurofibrillary plaques, and neuronal loss especially in the hippocampus and temporal regions. Medical management may reverse some of the symptoms but does not prevent disease progression. Parkinson's is a mainly sporadic degenerative disease with a gradual progressive course mainly affecting motor function more than memory. It was first described in 1817. This is a disease of the substantia nigra characterized by loss of melanin containing nerve cells and eosinophilic intracytoplasmic inclusions. Aside from emotional support and physical therapy, medical therapy is used to decrease tremors including anticholinergic drugs for tremors at onset, beta blockers for intention tremors, and levodopa for postural imbalance and akinesia. Deep brain stimulation is also used to treat symptoms later on as disease progresses. SNP starts in the same age range as Parkinson's (middle to later in life) that was first described in 1963 with disturbances in gait and balance secondary to rigidity of trunk muscles. Loss of neurons and gliosis is seen in the midbrain. Medical treatment is relatively unsuccessful. Multiple sclerosis is a demyelinating disease most often seen in young adults. The clinical manifestations are diverse and the progression can be chronic, acute, or remitting and relapsing. Medications and therapeutic plasma exchange have been used to treat this debilitating disease with limited efficacy. Clinical trials are ongoing looking at Mab therapies for treatment of these four neurologic degenerative diseases.

Multiple Sclerosis

Alemtuzumab (Lemtrada) is a humanized Mab (IgG1κ) targeting CD52 that depletes lymphocytes (B and T cell) as reported earlier and is FDA approved for treatment of acute relapsing and remitting multiple sclerosis. 292

Ocrelizumab (Ocrevus) is a humanized Mab (IgG1κ) with specificity to CD20 (a B-cell membrane protein). In phase II trials, there were decreases in brain lesions on imaging, and decrease rate of disability decline in primary progressive multiple sclerosis. 293

Natalizumab (Tysabri) is a monoclonal IgG4κ humanized antibody with specificity to cell adhesion molecule (CD62L) that is FDA approved for relapsing multiple sclerosis. 294 , 295

The mabs to watch out for in the future and are in clinical trials include anifrolumab a human monoclonal antibody in phase I trials; elezanumab is a human Mab (IgG1λ) with specificity to repulsive guidance molecule family member-A that is in phase II trials to be completed 2021; and finally inebilizumab (MEDI-551) is a humanized monoclonal antibody (IgG2κ) with specificity to CD19 (a B-cell lymphocyte protein). This Mab mechanism of action is via ADCC and has completed phase I trials with good safety profile and response in decreasing lesions seen on contrast enhanced magnetic resonance imaging. Otilimabis (MOR103) is a human Mab (IgG1λ) completing phase I studies with good safety profile that targets granulocyte-macrophage colony-stimulating factor. Ublituximab is in phase II clinical studies to be completed in 2019, and phase III studies are scheduled to be completed in 2021. This Mab is a chimeric Mab (IgG1κ) with specificity to CD20 MS2A1. 296 , 297 , 298 , 299 , 300

Additional Mab have serious adverse effects such as daclizumab a humanized monoclonal (IgG1κ) with specificity to (CD25 {IL-2Rα}); or are ineffective as is opicinumab a human Mab IgG1 with specificity to Leucine-rich repeat and immunoglobulin domain containing neurite outgrowth inhibitor receptor interacting protein-1 which in a phase II trial was no more beneficial than placebo in treating optic neuritis in multiple sclerosis patients. 301 , 302

Alzheimer's Disease

Aducanumab is a human Mab IgG1 with specificity to β-amyloid (N-terminus 3–6) soluble oligomers and insoluble fibers. Phase III clinical trials are ongoing since 2015.

BAN-2401 is a humanized Mab IgG1 with specificity to β-amyloid fibrillary and soluble β amyloid and is in phase IIb clinical studies since 2013.

Gosuranemab (BIIB092, IPN-007) is a humanized Mab IgG4κ with specificity to the tau protein and is in clinical trials to treat Alzheimer's disease scheduled to be completed in 2021. Gosuranemab is also in phase I studies to treat progressive suranuclear palsy and will be completed in 2020.

Crenezumab (RG7412, MABT5102A) is a humanized Mab IgG4 with specificity to 1–40 β-amyloid and is on phase III studies scheduled to be completed in 2021 and 2022.

Gantenerumab (R04909832, R1450) is a human Mab IgG1κ with targets β-amyloid. This Mab on initial phase III studies was found to be ineffective. Ongoing phase II/III trials are currently in place at higher dosing in a clinical population of people with autosomal dominant form of Alzheimer's disease.

Solanezumab (LY2062430) is a humanized Mab IgG1 with specificity to beta amyloid. Initial phase III trials discontinued for lack of efficacy in preventing Alzheimer's disease. Ongoing phase III trials are now in place for secondary prevention of this disease and will be completed in 2021 and 2022.

Mab antibodies studied and were ineffective include bapineuzumab, gantenerumab (R04909832, R1450), and ponezumab (RN1219, PF-04,360,365).

Parkinson's Disease

Prasinezumab (PRX002, RG7935, RO7046015) is a humanized Mab IgG1κ with specificity to α-synuclein. This Mab is in phase II clinical trials to treat Parkinson's and will be completed in 2021.

Allergic Diseases

Allergic reactions develop because of immunologic stimulation of IgE antibodies followed by their interaction with allergens and mast cells. Effects can be local (dermatitis) or systemic (respiratory, cardiovascular, and gastrointestinal). Treatment is either avoidance of the allergens or supportive therapy in acute allergic reactions including pharmacologic treatment with type 1 and 2 histamine blockers, glucocorticosteroids, and if life-threatening epinephrine. Passive antibody therapies are being studied and approved to curtail severe reactions.

Asthma

Asthma affects 24 million individuals in the US, and up to 10% of asthma patients have severe disease that may be uncontrolled despite high doses of standard-of-care asthma medications requiring additional use of chronic oral corticosteroids. Benralizumab (Fensenra) is a humanized Mab (IgG1κ) with specificity to CD125 (IL-5Rα). This Mab is approved to treat severe asthma of the eosinophilic subtype in ages 12 and older. Its mechanism of action is to decrease the number of eosinophils via ADCC. Basophils are also depleted. 303

Atopic Dermatitis

Dupilumab (Dupixent) is a human monoclonal gG4 antibody with specificity to interleukin-4 receptor subunit-alpha (IL-4Rα) that is approved to treat severe atopic dermatitis in adults. 304

Coagulopathy and Other Benign Hematologic Diseases

Coagulopathies are usually either autoimmune or genetic. In factor VIII deficiency, recombinant factor VIII is used to replace lack of this protein. However, patients may develop antibodies to factor VIII leading to high titers of inhibitors. Furthermore, patients without deficiency may also develop autoantibodies to factor VIII de novo leading to coagulopathies. Other factor combinations as well as recombinant active factors have been created to overcome these inhibitory antibodies. Mabs with bispecific binding are also being researched as another avenue for treatment.

ITP can lead to critical low platelet levels increasing risk for severe bleeding. ITP can occur in both adult and pediatric settings as it is considered an autoimmune disease. Typically, this is treated with steroids and IVIG. In addition, as mentioned earlier, RhD + patients have benefitted from polyclonal medications directed against the D antigen. Recently, Mab to treat this disease have been developed and will be discussed next.

Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that does not lead to bleeding but to development of diffuse thrombi in small blood vessels. More often, this disorder is secondary to an autoimmune inhibitory antibody to the disintegrin and metalloproteinase with thrombospondin type 1 motif member-13 (ADAMTS-13), known as acquired TTP. Inhibiting this zinc containing metalloprotease leads to lack of cleavage of large multimers of von Willebrand Factor (vWF). The large vWF multimers then more easily bind to platelets resulting in platelet clots in small blood vessels. More rarely, this disorder is secondary to an inherited deficiency of ADAMTS-13. This patient population with congenital deficiency is managed with transfusion of FFP to replace the deficient enzyme. Acquired TTP is typically treated with therapeutic plasma exchange (TPE). This treatment modality removes the inhibitory antibody and ultralarge vWF multimers. Similarly, TPE will replete the missing enzyme. Immunosuppressive agents may be added if only TPE is not effective. A Mab preventing interaction of vWF and platelets was recently approved for use in treating this disorder. 305 , 306 Caplacizumab-yhdp (Cablivi) is a humanized single-variable-domain immunoglobulin (Nanobody) that inhibits the interaction between ultralarge vWF multimers and platelets and is directed against vWF. It induces a faster response to therapy with TPE and decreases relapse with continued use during TPE. This medication is then used post-TPE treatment until immunological evidence of disease is controlled to prevent relapse. 305 , 307 , 308 This medication was FDA approved for use in TTP in 2019.

Atypical hemolytic uremic syndrome (aHUS) is a disorder of the complement system due to uncontrolled activation. This disorder presents with thrombocytopenia, thrombi, and renal dysfunction. Historically, this illness was treated with TPE; however, end-stage renal failure occurred in 30% of patients and about 65% mortality in subsequent relapses with increasing incidence of renal failure. There are now two monoclonal antibodies approved for the treatment of aHUS. Refer to Table 16.1 .

Sickle Pain Crisis

In sickle cell disease, one of the frequent complications is pain crises. This is usually treated with analgesics, oxygen, hydration, and transfusions (simple or exchange). Monoclonal antibodies are being developed to treat pain crises in sickle cell patients in both adult and pediatric populations. Crizanlizumab is a humanized Mab (IgG2κ) with specificity to selectin P. One phase II trial was completed in 2016 and three additional phase II studies will be completed between 2021 and 27 to treat vasoocclusive pain crisis. This medication may be under FDA review as early as 2019. 309 , 310

Infections

Antimicrobials have historically been developed against a variety of viral, bacterial, fungal, and parasitic infections. These pharmaceuticals target differences from human cells of these particular organisms such as cell wall or membrane structure, genetic make-up, transcription/translation of genetic material, or metabolic pathways. Often organisms develop resistance to entire categories of these medications. Earlier in the chapter, passive polyclonal antibodies were discussed in the treatment of some of these infectious agents and we will now discuss research in monoclonal therapies to pathogenic microorganisms.

Clostridium difficile

Enterocolitis from Clostridium difficile is a community or hospital acquired infection increasing morbidity and mortality in those that acquire it. Treatment is supportive or with fecal transplants or antibiotics. Bezlotoxumab (Zinplava) is a human Mab (IgG1) with specificity to Clostridium difficile 's B toxin. It is used to treat pseudomembranous colitis and prevent C. difficile reinfection. 311 , 312

Actoxumab, a monoclonal antibody against C. difficile toxin A, has shown not to be clinically significant.

Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infects almost all children by 2 years old and poses extra risk in preterm infants. Supportive therapy, RSV-IG or IVIG, and antiviral therapy have been used to mitigate the sequela of this infection with optimal response yet to be seen. No vaccines have yet to be developed for this infection. Recently, monoclonal antibodies have been FDA approved or are undergoing pre/clinical trials to treat this infectious process and include palivizumab, Nirsevimab (MEDI8897), TRL3d3 (3D3), and ALX-0171. 313 , 314

Not beneficial or safe in use for RSV: motavizumab, Suptavumab (REGN2222, SAR438584).

Influenza virus

Influenza is a worldwide respiratory infectious problem with cyclic epidemics yearly. Supportive therapy, yearly vaccinations, and antivirals are used to decrease the morbidity and mortality caused by this sometimes virulent pathogen. Both polyclonal and monoclonal therapies are being evaluated to better treat these infections. Mabs in pre/clinical trials include diridavumab (CR6262), firivumab, gedivumab (RG7745, RO6876802), lesofavumab (RG70026), and Navivumab (CT-P27).

Rabies

Rabies is a devastating viral infection with swift mortality if not treated quickly after initial exposure. Vaccines usually react too slowly and have to be combined with polyclonal IVIG infusions. Monoclonal therapy was previously studied but usually the virus mutates quickly and the infection is not controlled. More recently, in clinical trials, cocktails of Mabs are being tried to more closely mimic the benefits of polyclonal therapies. These Mabs include foravirumab, rafivirumab (CR57), and Rmab.

Hepatitis B virus

HBV is one of if not the most common infections in the world. Even though antivirals are available and effective, only recently they have they been widely used in the infant population and not just “high”-risk individuals. Mabs to treat this infection that are being investigated include libivirumab. Mab that is not found to be effective is tuvirumab.

Ebola

Ebola is a relatively rare but devastating hemorrhagic infection. Most care is supportive with various studies being performed to prevent/mitigate this disease. Vaccines are under development as well as passive polyclonal therapies. Mab therapies being developed or studied include porgaviximab (C2G4), cosfroviximab, and larcaviximab.

For these and other bacterial, fungal, and viral antiinfectious agents, information may be found in Table 16.1 .

Immunomodulation

In solid organ transplants, cellular or humoral immunity can develop against the transplant leading to acute or chronic rejection. An additional complication with these and stem cell transplants is severe GVHD. In the past, these transplant complications were treated with high-dose glucocorticosteroids, immunosuppressive medication, chemotherapeutic agents, IVIG, or T-cell lymphocytic specific immunoglobulins. Recently, Mabs have been added to this armamentarium to better control these adverse reactions to transplantations.

Basiliximab (Simulect) is a chimeric Mab (IgG1κ) with specificity to CD25 IL-2α. The only FDA-approved indication for this medication is prophylaxis of acute rejection in renal transplant patients. There are multiple ongoing studies of this biological for other organ transplants including liver, lung, and heart as well as for inflammatory/immunologic diseases such as GVHD following stem cell transplantation, ulcerative colitis, and uveitis. 315 , 316 , 317 , 318 , 319

Belatacept (Nulojix) is a soluble fusion protein consisting of the modified extracellular domain of CTLA-4 fused to the Fc domain of a recombinant human Mab IgG1. This Mab selectively inhibits T-cell activation through costimulation blockade binding to both CD80 and CD86 while blocking CD28 via tighter binding than its parent antibody abatacept. Refer to Table 16.1 .

Metabolic Syndromes

Hypercholesterolemia is associated with increased risk for cardiovascular disease/atherosclerosis secondary to inherited or dietary etiologies. Diet and exercise are used to treat mild forms of these disorders. Medications such as nicotinic acid, fibrates, bile acid binding resins, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors are used for more severe forms of these disorders. Phase III studies have been completed with monoclonal antibodies for patients' refractory to the previously mentioned forms of therapy.

Hypophosphatemia

Burosumab (KRN23, Crysvita) is a human Mab IgG1κ with specificity to phosphaturic hormone fibroblast growth factor 23 (FGF 23). This hormone is a regulator of phosphate and vitamin D homeostasis. FGF23 inhibits the enzyme CYP27B1 and stimulates CYP24A1, thereby reducing circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D. This medication is FDA approved for the treatment of X-linked hypophosphatemic rickets. 320 , 321

Osteoporosis

Denosumab (Prolia) is an FDA-approved human Mab (IgG2) that is a receptor activator of nuclear factor κB ligand that inhibits development and activity of osteoclasts. As Prolia, this medication is used to prevent or treat osteoporosis in women. 322 , 323 , 324 This medication under the trade name Xgeva is also used to prevent skeletal-related events in adults with bone metastasis from breast, prostate cancers, and multiple myeloma. 325 , 326

Endocrine Disorders

Diabetes may be classified as primary or secondary. In this chapter, we will be mainly interested in both insulin-dependent (Type I) and insulin-independent types (Type II). Type I diabetes mellitus is generally secondary to loss of β cells in the islets of Langerhans and subsequent loss of insulin production. Type II typically is secondary to decreased sensitivity to the effects of insulin. In type I, insulin is replaced exogenously depending on glucose levels. In type II, medications are given to stimulate islet cells to produce more insulin. Mabs are being developed to potentially mitigate the autoimmune process leading to Type I diabetes mellitus or the sequela of renal failure often seen with this disease. For type II, Mabs are being investigated to potentially decrease body mass index and thus decrease disease severity. Refer to Table 16.1 .

Other Clinical Disorders

Age-related macular degeneration (AMD) is the leading irreversible cause of visual loss affecting the elderly. Two forms include a dry form with deposits in the macula or a wet form involving abnormal growth of blood vessels. The wet form, even though less frequent, is associated with more severe visual acuity loss. Antiangiogenesic drugs or laser treatments are used to slow the progression or even partially reverse visual loss. Some trials have been completed while others are ongoing using Mab to treat the wet form of AMD. Brolucizumab was found as good as if not better than aflibercept in a phase III clinical trial. 327

Cryopyrin-associated periodic syndromes (including familial cold auto-inflammatory syndrome and Muckle-Wells syndrome); tumor necrosis factor receptor-associated periodic syndrome (TRAPS); hyperimmunoglobulin D Syndrome (HIDS)/mevalonate kinase deficiency and familial Mediterranean fever (FMF) may also respond to canakinumab. 328

Potential Future Uses of Monoclonal Antibodies and Their Targets

Passive antibody therapy continues to be useful clinically whether polyclonal or monoclonal therapy is implemented. Increased utilization of the classic polyclonal antibody preparations continue especially in the realm of infections. In the past 3 years, monoclonal therapy has evolved and revolutionized treatment in many areas. As targets are identified to modify disease pathology no matter its genre we continue to get a better handle on morbidity and mortality. We are learning that not only is the target important put the portion of the target mediating the effect we intend to modify is also important. Importantly, modification of antibodies to be more compatible with the immune system while decreasing rapidity of clearance also allows for more consistent therapy. There are also many targets yet to be discovered or only now being developed as in the canonical wingless/integrated (WNT) signaling. This receptor family is important in a multitude of diseases not limited to: hereditary colorectal cancer, various types of sporadic cancers, intellectual disability syndrome, Alzheimer's disease, bipolar disorder, bone diseases, and vascular diseases. One monoclonal antibody rosmantuzumab (OMP-131R10), a humanized Mab (IgG1κ), is in phase I trials to treat colorectal cancer. 329 , 330 Other disease processes have yet to find their optimal therapy (Alzheimer's) or are advancing to fuller therapeutic benefit. The future is wide open for this newer class of pharmaceuticals as they continue to develop to full fruition. Table 16.2 Summary of Polyclonal Antibody Therapies. Generic Drug Name Brand Name Additional Brand Names AHFS Classification Dosage Form(s) Restricted Medication Antithymocyte globulin (equine) Atgam Immunosuppressive agent Intravenous solution Antithymocyte globulin (rabbit) Thymoglobulin Immunosuppressive agent Intravenous solution Antivenin Latrodectus mactans Black widow Antivenin Serums Intravenous solution Antivenin micrurus Eastern and Texas coral Snake Antivenin Serums Intravenous solution Botulism immune globulin BabyBIG Crotalidae polyvalent immune Fab Crofab Serums Intravenous solution Cytomegalovirus immune globulin Cytogam Serums Intravenous solution Yes Digoxin immune Fab Digibind Serums Intravenous solution Hepatitis B immune globulin Hepagam-B Serums Intramuscular solution, Intravenous solution Hepatitis B immune globulin BayHepB HepaGam B, Hyper Hep B, Nabi-HB High antibody titer Ebola FFP High antibody titer influenza FFP Immunoglobulin (generic) Gamunex Vivaglobin, Cuvitru, Privigen, gammagard, octagam, gamunex, hizentra, Bivigam, Carimune, Flebogamma, Gamastan, Gamimune, Gammaplex, gammar, Panglobulin, Panzyga, Sandoglobulin Intravenous, Subcutaneous Treat XLA, CVID, Hyper IgM syndromes, Wiskott Aldrich syndrome Rabies immune globulin Bayrab HyperRAB, Imogam rabies, KedRAB Respiratory syncytial virus immune globulin RespiGam Rho (D) immune globulin WhinRho RhoGam Rhophylac, MicRhoGAM, BatRhoD, HyperRho Serums Intravenous, intramuscular solutions Rimabotulinumtoxin B Myobloc Other Miscellaneous Therapeutic agents Injection solution Yes Rozrolimupab Anti-RhD Prevent isoimmunization ITP Tetanus immune globulin Baytet Hypertet Varicella zoster immune globulin VariZIG Searched sites for table information. Monoclonal. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm . https://fdasis.nlm.nih.gov/srs/ . https://clinicaltrials.gov/ct2/ . https://www.ncbi.nlm.nih.gov/pubmed/ . https://chem.nlm.nih.gov/chemidplus/rn . https://druginfo.nlm.nih.gov/drugportal/ . https://www.creativebiolabs.net/ .

References

1 Sangstat Medical Corporation Thymoglobulin; (Anti-thymocyte Globulin [rabbit]) Prescribing Information Menlo Park, CA December 1998

2 Ormrod D. Jarvis B. Antithymocyte globulin (rabbit): a review of the use of Thymoglobulin in the prevention and treatment of acute renal allograft rejection BioDrugs 14 2000 255 273

3 Kalamazoo, MI Pharmacia. Atgam Prescribing Information June 2000

4 The Upjohn Company Drug Reference: Atgam Kalamazoo, MI November 1981

5 Cosimi A.B. The clinical value of antilymphocyte antibodies Transplant Proc 13 1981 462 468 7022874

6 Cosimi A.B. The clinical usefulness of antilymphocyte antibodies Transplant Proc 15 1983 583 589

7 Cho S.I. Bradley J.W. Carpenter C.B. Antithymocyte globulin, pretransplant blood transfusion, and tissue typing in cadaver kidney transplantation Am J Surg 145 1983 464 471 6340551 10.1016/0002-9610(83)90041-7

8 Nelson P.W. Cosimi A.B. Delmonico F.L. Antithymocyte globulin as the primary treatment for renal allograft rejection Transplantation 36 1983 587 589 6356523

9 Nowygrod R. Appel G. Hardy M.A. Use of ATG for reversal of acute allograft rejection Transplant Proc 13 1981 469 472 7022875

10 Hardy M.A. Nowygrod R. Elberg A. Use of ATG in treatment of steroid-resistant rejection Transplantation 29 1980 162 164 6986690 10.1097/00007890-198002000-00015

11 Simonian S.J. Lyons P. Chvala R. Reversal of acute cadaveric renal allograft rejection with added ATG treatment Transplant Proc 15 1983 604 607

12 Gaber A.O. First M.R. Tesi R.J. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation Transplantation 66 1998 29 37 9679818 10.1097/00007890-199807150-00005

13 Brennan D.C. Flavin K. Lowell J.A. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients Transplantation 67 1999 1011 1018 10221486 10.1097/00007890-199904150-00013

14 Lance E.M. Mode of action of antilymphocyte serum Fed Proc 29 1970 209 211 4904625

15 Martin W.J. Miller J.F.A.P. Site of action of antilymphocyte globulin Lancet 2 1967 1285 1287 4168616 10.1016/s0140-6736(67)90395-9

16 Levey R.H. Medawar P.B. Nature and mode of action of antilymphocytic antiserum Proc Natl Acad Sci USA 56 1966 1130 1137 5339289 10.1073/pnas.56.4.1130 PMC220018

17 Wohlman M.H. Toledo-Pereyra L.H. Zeichner W.D. The immunosuppressive properties of antilymphocyte serum preparations: a current review Dial Transplant 10 1981 19 28

18 Zimmerman B. Tsui F. Immunosuppressive antilymphocyte serum: different subpopulations of T lymphocytes are influenced at different doses of antilymphocyte serum Transplantation 28 1979 323 328 315628 10.1097/00007890-197910000-00012

19 Bach J.F. Mechanism and significance of rosette inhibition by antilymphocyte serum Bach J.F. Dormont J. Eyquem A. International Symposium on Antilymphocyte Serum; Symposium Series on Immunobiology Standardization Vol. 16 1970 S Karger New York 189 198

20 Pirofsky B. Beaulieu R. Bardana E.J. Antithymocyte antiserum effects in man Am J Med 56 1974 290 296 4130597 10.1016/0002-9343(74)90610-x

21 Greco B. Bielory L. Stephany D. Antithymocyte globulin reacts with many normal human cell types Blood 62 1983 1047 1054 6354303

22 Bonifazi F, Solano C, Wolschke C et al. GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute leukaemia in remission: final results of quality of life and long-term outcome analysis of a phase 3 randomised study. The Lancet. Hematology, ISSN: 2352-3026, Vol: 6, Issue: 2, Page: e89-e99. 10.1016/S2352-3026(18)30214-X 30709437

23 Champlin RE. Treatment of aplastic anemia, pp. 480–483. In: Gale R.P. moderator Aplastic anemia: biology and treatment Ann Intern Med 95 1981 477 494 6116472 10.7326/0003-4819-95-4-477

24 Champlin R. Ho W. Gale R.P. Antithymocyte globulin treatment in patients with aplastic anemia N Engl J Med 308 1983 113 118 6336819 10.1056/NEJM198301203080301

25 Cheeseman S.H. Rubin R.H. Stewart J.A. Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation: effects on cytomegalovirus and herpes simplex virus infections N Engl J Med 300 1979 1345 1349 220536 10.1056/NEJM197906143002401

26 Cheeseman S.H. Henle W. Rubin R.H. Epstein-Barr virus infection in renal transplant recipients: effects of antithymocyte globulin and interferon Ann Intern Med 93 Part 1 1980 39 42 6156614 10.7326/0003-4819-93-1-39

27 Diethelm A.G. Aldrete J.S. Shaw J.F. Clinical evaluation of equine antithymocyte globulin in recipients of renal allografts: analysis of survival, renal function, rejection, histocompatibility, and complications Ann Surg 180 1974 20 28 4599406 10.1097/00000658-197407000-00004 PMC1343604

28 Talecris Biotherapeutics HyperTET S/D (Tetanus Immune Globulin [human]) Solvent/detergent Treated Prescribing Information May 2008 Research Triangle Park NC

29 Centers for Disease Control and Prevention General recommendations on immunization: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 RR-15 2006 1 48 17136024

30 Murphy T.V. Slade B.A. Broder K.R. Prevention of pertussis, tetanus, and diphtheria among pregnant and postpartum women and their infants recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 57 2008 1 51 18509304

31 Centers for Disease Control and Prevention Epidemiology and Prevention of Vaccine-Preventable Diseases 11th ed. 2009 Public Health Foundation Washington, DC

32 CSL Behring CytoGam (Cytomegalovirus Immune Globulin Intravenous [human][CMV-IG]) Liquid Formulation Solvent Detergent Treated Prescribing Information Kankakee, IL November 2010

33 Snydman D.R. McIver J. Leszczynski J. A pilot trial of a novel cytomegalovirus immune globulin in renal transplant recipients Transplantation 38 1984 553 557 6093299 10.1097/00007890-198411000-00026

34 Snydman D.R. Werner B.G. Heinze-Lacey B. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients N Engl J Med 317 1987 1049 1054 2821397 10.1056/NEJM198710223171703

35 Snydman D.R. Prevention of cytomegalovirus-associated diseases with immunoglobulin Transplant Proc 23 Suppl 3 1991 131 135 1648817

36 Snydman D.R. Werner B.G. Tilney N.L. Final analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus-immune globulin: comparison of the randomized and open-label trials Transplant Proc 23 1991 1357 1360 1846464

37 Werner B.G. Snydman D.R. Freeman R. Cytomegalovirus immune globulin for the prevention of primary CMV disease in renal transplant patients: analysis of usage under treatment IND status Transplant Proc 25 1993 1441 1443 8382875

38 Ho M. Cytomegalovirus Mandell G.L. Bennett J.E. Dolin R. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases 4th ed. 1995 Churchill Livingstone New York 1351 1364

39 Dickinson B.I. Gora-Harper M.L. McCraney S.A. Studies evaluating high-dose acyclovir, intravenous immune globulin, and cytomegalovirus hyperimmunoglobulin for prophylaxis against cytomegalovirus in kidney transplant recipients Ann Pharmacother 30 1996 1452 1464 8968459 10.1177/106002809603001215

40 Snydman D.R. Cytomegalovirus immunoglobulins in the prevention and treatment of cytomegalovirus disease Clin Infect Dis 12 Suppl 7 1990 S839 S848 10.1093/clinids/12.supplement_7.s839 2173113

41 Patel R. Snydman D.R. Rubin R.H. Cytomegalovirus prophylaxis in solid organ transplant recipients Transplantation 61 1996 1279 1289 8629285 10.1097/00007890-199605150-00001

42 Meyers J.D. Prevention of cytomegalovirus infection after marrow transplantation Rev Infect Dis 11 Suppl 7 1989 S1691 S1705 ([PubMed]) 2557664 10.1093/clinids/11.supplement_7.s1691

43 Winston D.J. Ho W.G. Champlin R.E. Cytomegalovirus infections after allogeneic bone marrow transplantation Clin Infect Dis 12 Suppl 7 1990 S776 S787 10.1093/clinids/12.supplement_7.s776 2173107

44 Valantine H.A. Prevention and treatment of cytomegalovirus disease in thoracic organ transplant patients: evidence for a beneficial effect of hyperimmune globulin Transplant Proc 27 Suppl 1 1995 49 57 7482821

45 Grundy J.E. Virologic and pathogenetic aspects of cytomegalovirus infection Clin Infect Dis 12 Suppl 7 1990 S711 S719 10.1093/clinids/12.supplement_7.s711 2173100

46 Bass E.B. Powe N.R. Goodman S.N. Efficacy of immune globulin in preventing complications of bone marrow transplantation: a meta-analysis Bone Marrow Transplant 12 1993 273 282 8241987

47 Taylor-Wiedeman J. Sissons J.G. Borysiewicz L.K. Sinclair J.H. Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells J Gen Virol 72 1991 2059 2064 1654370 10.1099/0022-1317-72-9-2059

48 Tsinontides A.C. Bechtel T.P. Cytomegalovirus prophylaxis and treatment following bone marrow transplantation Ann Pharmacother 30 1996 1277 1290 8913411 10.1177/106002809603001113

49 Zamora M.R. Fullerton D.A. Campbell D.N. Use of cytomegalovirus (CMV) hyperimmune globulin for prevention of CMV disease in CMV-seropositive lung transplant recipients Transplant Proc 26 Suppl 1 1994 49 51 7940974

50 Snydman D.R. Werner B.G. Dougherty N.N. A further analysis of the use of cytomegalovirus immune globulin in orthotopic liver transplant patients at risk for primary infection Transplant Proc 26 Suppl 1 1994 23 27 7940972

51 Aguado J.M. Gomez-Sanchez M.A. Lumbreras C. Prospective randomized trial of efficacy of ganciclovir versus that of anti-cytomegalovirus (CMV) immunoglobulin to prevent CMV-seropositive heart transplant recipients treated with OKT3 Antimicrob Agents Chemother 39 1995 1643 1645 7492123 10.1128/aac.39.7.1643 PMC162800

52 Merck & Co Inc. Antivenin (Latrodectus Mactans) (Black Widow Spider Antivenin) Equine Origin Prescribing Information Whitehouse Station, NJ February 2014

53 Clark R.F. Wethern-Kestner S. Vance M.V. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases Ann Emerg Med 21 1992 782 787 1351707 10.1016/s0196-0644(05)81021-2

54 Wyeth Laboratories Inc Antivenin ( Micrurus fulvius ) (Equine Origin) (North American Coral Snake Antivenin) Prescribing Information Marietta, PA August 2001

55 The United States Pharmacopeia, 25th Rev, and the National Formulary 20th ed. 2002 The United States Pharmacopeial Convention, Inc Rockville, MD 158

56 Protherics Inc Crofab (Crotalidae Polyvalent Immune Fab [ovine]) Prescribing Information Brentwood, TN 2010 Sep

57 Parrish H.M. Bites by coral snakes: report of 11 representative cases Am J Med Sci 253 1967 561 4960877

58 Identification and distribution of North American venomous snakes Russell F.E. Snake Venom Poisoning 1980 JB Lippincott Company Philadelphia 45 86

59 Roze J.A. New world coral snakes (Elapidae): a taxonomic and biologic summary Mem Inst Butantan, Sao Paulo. 46 1982 305 338

60 Anon Treatment of snakebite in the USA Med Lett Drugs Ther 24 1982 87 89 7110058

61 Clark R.F. McKinney P.E. Chase P.B. Immediate and delayed allergic reactions to Crotalidae polyvalent immune Fab (ovine) antivenom Ann Emerg Med 39 2002 671 676 12023714 10.1067/mem.2002.123134

62 Lavonas E.J. Ruha A.M. Banner W. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop BMC Emerg Med 11 2011 2 21291549 10.1186/1471-227X-11-2 PMC3042971

63 England PH. MERS-CoV: clinical decision making support for treatment. https://www.gov.uk/government/publications/mers-covclinical-decision-making-support-for-treatment (accessed Nov 8, 2016).

64 Luke T.C. Kilbane E.M. Jackson J.L. Hoffman S.L. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 145 2006 599 609 16940336 10.7326/0003-4819-145-8-200610170-00139

65 Hung I.F. To K.K. lee C.K. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection Clin Infect Dis 52 2011 447 456 21248066 10.1093/cid/ciq106 PMC7531589

66 Gulland A. First Ebola treatment is approved by WHO BMJ 349 2014 g5539 25200068 10.1136/bmj.g5539

67 Mupapa K. Massamba M. Kibadi K. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. International Scientific and Technical Committee J Infect Dis 179 1999 S18 S23 9988160 10.1086/514298

68 Klein H.G. Should blood be an essential medicine? N Engl J Med 368 2013 199 201 23323895 10.1056/NEJMp1213134

69 Ala F. Allain J.P. Bates I. External financial aid to blood transfusion services in sub-Saharan Africa: a need for reflection PLoS Med 9 2012 e1001309 22984355 10.1371/journal.pmed.1001309 PMC3439367

70 Burnouf T. Emmanuel J. Mbanya D. Ebola: a call for blood transfusion strategy in sub-Saharan Africa Lancet 384 2014 1347 1348 25277678 10.1016/S0140-6736(14)61693-7

71 GlaxoSmithKline. Digibind (Digoxin Immune Fab [ovine]) Prescribing Information September 2003 Research Triangle Park NC

72 Smith T.W. Haber E. Yeatman L. Reversal of advanced digoxin intoxication with Fab fragments of digoxin-specific antibodies N Engl J Med 294 1976 797 800 943040 10.1056/NEJM197604082941501

73 Smith T.W. Butler V.P. Haber E. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments N Engl J Med 307 1982 1357 1362 6752715 10.1056/NEJM198211253072201

74 Cole P.L. Smith T.W. Use of digoxin-specific Fab fragments in the treatment of digitalis intoxication Drug Intell Clin Pharm 20 1986 267 270 3698816 10.1177/106002808602000403

75 Smith T.W. Butler V.P. Haber E. Cardiac glycoside-specific antibodies in the treatment of digitalis intoxication Haber E. Krause R.M. Antibodies in Human Diagnosis and Therapy 1977 Raven Press New York 365 389

76 Wenger T.L. Butler V.P. Haber E. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments J Am Coll Cardiol 5 1985 118 123A 3886748 10.1016/s0735-1097(85)80471-x

77 Larbig D. Raff U. Haasis R. Reversal of digitalis effects by specific antibodies Pharmacology 18 1979 1 8 368816 10.1159/000137223

78 Smolarz A. Roesch E. Lenz E. Digoxin specific antibody (Fab) fragments in 34 cases of severe digitalis intoxication J Toxicol Clin Toxicol 23 1985 327 340 4057323 10.3109/15563658508990641

79 Protherics Inc Digifab (Digoxin Immune Fab [ovine]) Prescribing Information Brentwood, TN September 2010

80 Smith T.W. Use of antibodies in the study of the mechanism of action of digitalis Ann N Y Acad Sci 242 1974 731 736 4279618 10.1111/j.1749-6632.1974.tb19134.x

81 Watson J.F. Butler V.P. Biologic activity of digoxin-specific antisera J Clin Investig 51 1972 638 648 ([PubMed]) 5011105 10.1172/JCI106853 PMC302170

82 Butler V.P. Antibodies as specific antagonists of toxins, drugs, and hormones Pharmacol Rev 34 1982 109 114 7041142

83 Gardner J.D. Kiino D.R. Swartz T.J. Effects of digoxin-specific antibodies on accumulation and binding of digoxin by human erythrocytes J Clin Investig 52 1973 1820 1833 4719664 10.1172/JCI107364 PMC302462

84 Sullivan J.B. Immunotherapy in the poisoned patient Med Toxicol 1 1986 47 60 3537615 10.1007/BF03259827

85 Boucher B.A. Lalonde R.L. Digoxin-specific antibody fragments for the treatment of digoxin intoxication Clin Pharm 5 1986 826 827 3780152

86 Schmidt D.H. Butler V.P. Reversal of digoxin toxicity with specific antibodies J Clin Investig 50 1971 1738 1744 4106462 10.1172/JCI106663 PMC442074

87 Butler V.P. Schmidt D.H. Smith T.W. Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs J Clin Investig 59 1977 345 349 299860 10.1172/JCI108647 PMC333366

88 Curd J.G. Smith T.W. Jaton J.C. The isolation of digoxin-specific antibody and its use in reversing the effects of digoxin Proc Natl Acad Sci USA 68 1971 2401 2406 5289875 10.1073/pnas.68.10.2401 PMC389431

89 Nisonoff A. Enzymatic digestion of rabbit gamma globulin and antibody and chromatography of digestion products Methods Med Res 10 1964 134 141 14284906

90 Lapostolle F. Borron S.W. Verdier C. Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning Crit Care Med 36 2008 3014 3018 18824911 10.1097/CCM.0b013e31818b341c

91 Eyal D. Molczan K.A. Carroll L.S. Digoxin toxicity: pediatric survival after asystolic arrest Clin Toxicol 43 2005 51 54 10.1081/clt-45025 15732447

92 Bateman D.N. Digoxin-specific antibody fragments: how much and when? Toxicol Rev 23 2004 135 143 15862081 10.2165/00139709-200423030-00001

93 Schaeffer T.H. Mlynarchek S.L. Stanford C.F. Treatment of chronically digoxin-poisoned patients with a newer digoxin immune fab--a retrospective study J Am Osteopath Assoc 110 2010 587 592 21068223

94 Ip D. Syed H. Cohen M. Digoxin specific antibody fragments (Digibind) in digoxin toxicity BMJ 339 2009 b2884 19729422 10.1136/bmj.b2884

95 Flanagan R.J. Jones A.L. Fab antibody fragments: some applications in clinical toxicology Drug Saf 27 2004 1115 1133 15554746 10.2165/00002018-200427140-00004

96 Ware J.A. Young J.B. Luchi R.J. Treatment of severe digoxin toxicity with digoxin-specific antibodies: a case report Tex Med 79 1983 57 59 6829019

97 Nicholls D.P. Murtagh J.G. Holt D.W. Use of amiodarone and digoxin specific Fab antibodies in digoxin overdosage Br Heart J 53 1985 462 464 3986060 10.1136/hrt.53.4.462 PMC481789

98 Centers for Disease Control and Prevention General recommendations on immunization: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 RR-15 2006 1 47 17136024

99 American Academy of Pediatrics 2006 Red Book: Report of the Committee on Infectious Diseases 27th ed. 2006 American Academy of Pediatrics Elk Grove Village, IL

100 Talecris HyperHEP B S/D (Hepatitis B Immune Globulin [human] Solvent/detergent Treated) Prescribing Information June 2007

101 Nabi Nabi-HB (Hepatitis B Immune Globulin [human] Solvent/detergent Treated and Filtered) Prescribing Information Boca Raton, FL June 2003

102 Centers for Disease Control and Prevention A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part I: immunization of infants, children, and adolescents MMWR Recomm Rep (Morb Mortal Wkly Rep) 54 RR-16 2005 1 33 16371945

103 Centers for Disease Control and Prevention A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Part II: immunization in adults MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 RR-16 2006 1 33 17159833

104 Apotex HepaGam B (Hepatitis B Immune Globulin Intravenous [human]) Prescribing Information Weston, FL April 2007

105 American Academy of Pediatrics 2006 Red Book: Report of the Committee on Infectious Diseases 27th ed. 2006 American Academy of Pediatrics Elk Grove Village, IL

106 Centers for Disease Control and Prevention Recommended immunization schedules for persons 0 through 18 years–United States, 2009 MMWR Morb Mortal Wkly Rep 57 2009 Q1-4

107 Centers for Disease Control Immunization Practices Advisory Committee (ACIP) Protection against viral hepatitis: recommendations of the immunization practices advisory committee (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 39 RR-2 1990 1 26 2153904

108 Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 RR-11 2006 1 94 16888612

109 Centers for Disease Control and Prevention Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis MMWR Morb Mortal Wkly Rep 50 No. RR-11 2001 1 51 11442229

110 Coffin C.S. Terrault N.A. Management of hepatitis B in liver transplant recipients J Viral Hepat 14 Suppl1 2007 37 44 17958641 10.1111/j.1365-2893.2007.00916.x

111 Yilmaz N. Shiffman M.L. Stravitz R.T. Prophylaxis against recurrence of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years Liver Int 28 2008 72 78 17983429 10.1111/j.1478-3231.2007.01611.x

112 Gish R.G. McCashland T. Hepatitis B in liver transplant recipients Liver Transplant 12 2006 S54 S64 10.1002/lt.20950 17051551

113 Anderson R.D. Chinnakotla S. Guo L. Intramuscular hepatitis B immunoglobulin (HBIG) and nucleosides for prevention of recurrent hepatitis B following liver transplantation: comparison with other HBIG regimens Clin Transplant 21 2007 510 517 17645711 10.1111/j.1399-0012.2007.00678.x

114 Gane E.J. Angus P.W. Strasser S. Lamivudine plus low-dose hepatitis B immunoglobulin to prevent recurrent hepatitis B following liver transplantation Gastroenterology 132 2007 931 937 17383422 10.1053/j.gastro.2007.01.005

115 Nath D.S. Kalis A. Nelson S. Hepatitis B prophylaxis post-liver transplant without maintenance hepatitis B immunoglobulin therapy Clin Transplant 20 2006 206 210 16640528 10.1111/j.1399-0012.2005.00467.x

116 Eisenbach C. Sauer P. Mehrabi A. Prevention of hepatitis B virus recurrence after liver transplantation Clin Transplant 20 Suppl 2006 111 116 17100710 10.1111/j.1399-0012.2006.00609.x

117 Zheng S. Chen Y. Liang T. Prevention of hepatitis B recurrence after liver transplantation using lamivudine or lamivudine combined with hepatitis B immunoglobulin prophylaxis Liver Transplant 12 2006 253 258 10.1002/lt.20701 16447195

118 Cangene Corporation Varizig Varicella Zoster Immune Globulin (Human) Lyophilized Powder for Solution for Injection for Intramuscular Administration Only Prescribing Information Winnipeg, Canada December 2012

119 Centers for Disease Control and Prevention Prevention of varicella: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 56 RR-4 2007 1 40 17585291

120 National Center for Immunization and Respiratory Diseases General recommendations on immunization --- recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 60 2011 1 64 21293327

121 American Academy of Pediatrics Red Book: 2009 Report of the Committee on Infectious Diseases 28th ed. 2009 American Academy of Pediatrics Elk Grove Village, IL

122 Centers for Disease Control and Prevention (CDC) FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella MMWR Morb Mortal Wkly Rep 61 2012 212 22456121

123 Solstice Neurosciences Myobloc (rimabotulinumtoxinB) Injection Prescribing Information South San Francisco, CA May 2010

124 Brashear A. Lew M.F. Dykstra D.D. Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia Neurology 53 1999 1439 1446 10534248 10.1212/wnl.53.7.1439

125 Terranova W. Breman J.G. Locey R.P. Botulism type B: epidemiologic aspects of an extensive outbreak Am J Epidemiol 108 1978 150 156 707476 10.1093/oxfordjournals.aje.a112599

126 Cheng C.M. Chen J.S. Patel R.P. Unlabeled uses of botulinum toxins: a review, part 1 Am J Health Syst Pharm 63 2006 145 152 16390928 10.2146/ajhp050137

127 Allergan Botox (onabotulinumtoxinA) for Injection Prescribing Information Irvine, CA September 2013

128 Bell M.S. Vermeulen L.C. Sperling K.B. Pharmacotherapy with botulinum toxin: harnessing nature's most potent neurotoxin Pharmacotherapy 20 2000 1079 1091 10999501 10.1592/phco.20.13.1079.35040

129 Tsui J.K. Botulinum toxin as a therapeutic agent Pharmacol Ther 72 1996 13 24 8981568 10.1016/s0163-7258(96)00091-5

130 Moore A.P. Botulinum toxin A (BoNT-A) for spasticity in adults. What is the evidence? Eur J Neurol 9 Suppl 1 2002 42 47 11918649 10.1046/j.1468-1331.2002.0090s1042.x

131 Corry I.S. Cosgrove A.P. Duffy C.M. Botulinum toxin A compared with stretching casts in the treatment of spastic equinus: a randomised prospective trial J Pediatr Orthop 18 1998 304 311 9600553

132 Figgit D.P. Noble S. Botulinum toxin B: a review of its therapeutic potential in the management of cervical dystonia Drugs 62 2002 705 722 11893235 10.2165/00003495-200262040-00011

133 Lew M.F. Adornato B.T. Duane D.D. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia Neurology 49 1997 701 707 9305326 10.1212/wnl.49.3.701

134 Anon Botulinum toxin for cervical dystonia Med Lett Drugs Ther 43 2001 63 64 11468603

135 California Department of Public Health BabyBIG (Botulism Immune Globulin Intravenous [human]) Prescribing Information Richmond, CA January 2012

136 Arnon S.S. Creation and development of the public service orphan drug Human Botulism Immune Globulin Pediatrics 119 2007 785 789 ([PubMed]) 17403850 10.1542/peds.2006-0646

137 Infant Botulism Treatment and Prevention Program. Division of Communicable Disease Control, California Department of Health Services. From IBTPP website. Accessed 2012 Mar 26. [Web].

138 Underwood K. Rubin S. Deakers T. Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Childrens Hospital Los Angeles Pediatrics 120 2007 e1380 e1385 ([PubMed]) 18055655 10.1542/peds.2006-3276

139 Arnon S.S. Infant botulism Feigin R.D. Cherry J.D. Demmler-Harrison G.J. Feigin: Feigin and Cherry's Textbook of Pediatric Infectious Diseases 6th ed. 2009 Saunders Elsevier Philadelphia, PA

140 Arnon S.S. Schechter R. Maslanka S.E. Human botulism immune globulin for the treatment of infant botulism N Engl J Med 354 2006 462 471 16452558 10.1056/NEJMoa051926

141 Talecris Biotherapeutics, Inc HyperRAB S/D (Rabies Immune Globulin [human] Solvent/detergent Treated) Prescribing Information March 2008 Research Triangle Park NC

142 Sanofi Pasteur Imogam Rabies-HT (Rabies Immune Globulin [human] USP, Heat Treated) Prescribing Information Swiftwater, PA December 2005

143 Centers for Disease Control and Prevention Human rabies prevention—United States, 2008. Recommendations of the advisory committee on immunization practices MMWR Recomm Rep (Morb Mortal Wkly Rep) 57 RR-3 2008 1 27 18496505

144 Centers for Disease Control and Prevention Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies. Recommendations of the Advisory Committee on Immunization Practices MMWR Recomm Rep (Morb Mortal Wkly Rep) 59 RR-2 2010 1 9 20300058

145 Cangene bioPharma WinRho SDF (Rho [D] Immune Globulin Intravenous [human]) Prescribing Information Baltimore, MD December 2010

146 Grifols Therapeutics HyperRHO S/D Mini-Dose (Rho [D] Immune Globulin [human]) Prescribing Information September 2012 Research Triangle Park NC

147 Ortho-Clinical Diagnostics Rho-GAM (Rho [D] Immune Globulin [human]) Ultra-filtered PLUS and MICRhoGAM (Rho [D] Immune Globulin [human]) Ultra-filtered PLUS Prescribing Information November 2012 Raritan NJ

148 The United States pharmacopeia 23rd Rev, and the National Formulary 18th ed. 1995 The United States Pharmacopeial Convention, Inc Rockville, MD 350

149 CSL Behring Rhophylac (Rho [D] Immune Globulin Intravenous [human]) Prescribing Information October 2012 Kankakee IL

150 Kumar S. Universal RDH genotyping in fetuses BMJ 336 2008 783 18390495 10.1136/bmj.39533.358252.BE PMC2292275

151 Bussel J.B. Graziano J.N. Kimberly R.P. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect Blood 77 1991 1884 1893 1850307

152 Becker T. Küenzlen E. Salama A. Treatment of childhood idiopathic thrombocytopenic purpura with Rhesus antibodies (anti-D) Eur J Pediatr 145 1986 166 169 3021462 10.1007/BF00446055

153 Andrew M. Blanchette V.S. Adams M. A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D J Pediatr 120 1992 522 527 1313096 10.1016/s0022-3476(10)80001-0

154 Scaradavou A. Woo B. Woloski B.M.R. Intravenous anti-D treatment of immune thrombocytopenic 20. Ballow M. Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases Cancer 68 1991 1430 1436 1878841 10.1002/1097-0142(19910915)68:6+<1430::aid-cncr2820681405>3.0.co;2-4

155 Ballow M. Mechanisms of action of intravenous immunoglobulin therapy and potential use in autoimmune connective tissue diseases Cancer 68 1991 1430 1436 1878841 10.1002/1097-0142(19910915)68:6+<1430::aid-cncr2820681405>3.0.co;2-4

156 Kniker W.T. Immunosuppressive agents, γ-globulin, immunomodulation, immunization, and aphresis J Allergy Clin Immunol 84 1989 1104 1107 2480974 10.1016/0091-6749(89)90163-2

157 Blanchette V. Imbach P. Andrew M. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura Lancet 344 1994 703 707 7915773 10.1016/s0140-6736(94)92205-5

158 Berchtold P. McMillan R. Therapy of chronic idiopathic thrombocytopenic purpura in adults Blood 74 1989 2309 2317 2478227

159 Rodeghiero F. Schiavotto C. Castaman G. A follow-up study of 49 adult patients with idiopathic thrombocytopenic purpura treated with high-dose immunoglobulins and anti-D immunoglobulins Haematologica 77 1992 248 252 1330848

160 Stasi R. Stipa E. Masi M. Long-term observation of 208 adults with chronic idiopathic thrombocytopenic purpura Am J Med 98 1995 436 442 7733121 10.1016/s0002-9343(99)80342-8

161 Landonio G. Galli M. Nosari A. HIV-related severe thrombocytopenia in intravenous drug-users: prevalence, response to therapy in a medium-term follow-up, and pathogenetic evaluation AIDS 4 1990 29 34 2156528

162 Hoffman D.M. Caruso R.F. Mirando T. Human immunodeficiency virus-associated thrombocytopenia Dicp Ann Pharmacother 1989 157 160 10.1177/106002808902300212 2658372

163 Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Silver Spring, MD. From FDA website ( http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm ). Accessed 2013 Jul 2.

164 Oksenhendler E. Bierling P. Brossard Y. Anti-RH immunoglobulin therapy for human immunodeficiency virus-related immune thrombocytopenic purpura Blood 71 1988 1499 1502 2833961

165 Okwundu C.I. Afolabi B.B. Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy Cochrane Database Syst Rev 1 2013 CD007885 10.1002/14651858.CD007885.pub2 PMC11694612 23440818

166 CSL Behring Carimune NF, Nanofiltered (Immune Globulin Intravenous [human] Lyophilized for Solution) Prescribing Information November 2016 Kankakee IL

167 Baxalta US Inc Gammagard S/D (Immune Globulin Intravenous [human] IgA Less than or Equal to 2.2 mcg/mL in a 5% Solution) Prescribing Information Westlake Village, CA September 2016

168 Grifols USA GamaSTAN S/D (Immune Globulin IM [human]) Prescribing Information June 2017 Research Triangle Park NC

169 Octapharma USA Octagam (Immune Globulin Intravenous [human] 5% Liquid) Prescribing Information Hoboken, NJ August 2015

170 Grifols Therapeutics Inc Gamunex-C (Immune Globulin Intravenous [human] 10% Caprylate/chromatography Purified) Prescribing Information September 2016 Research Triangle Park NC

171 Baxalta US Inc Gammagard S/D (Immune Globulin Intravenous [human] IgA Less than 1 mcg/mL in a 5% Solution) Prescribing Information Westlake Village, CA September 2016

172 CSL Behring Privigen (Immune Globulin Intravenous [human] 10% Liquid) Prescribing Information Kankakee, IL October 2016

173 American Academy of Pediatrics Red Book: 2015 Report of the Committee on Infectious Diseases 30th ed. 2015 American Academy of Pediatrics Elk Grove Village, IL

174 NIH Consensus Development Conference. Intravenous immunoglobulin: prevention and treatment of disease J Am Med Assoc 264 1990 3189 3193 2255028

175 Hughes R.A. Donofrio P. Bril V. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial Lancet Neurol 7 2008 136 144 18178525 10.1016/S1474-4422(07)70329-0

176 CSL Behring Hizentra (Immune Globulin Subcutaneous [human] 20% Liquid) Prescribing Information Kankakee, IL October 2016

177 Bio Products Laboratory (distributed by BPL Inc) Gammaplex (Immune Globulin Intravenous [human] 5% Liquid for Intravenous Use) Prescribing Information Hertfordshire, UK September 2015

178 Biotest Pharmaceuticals Bivigam (Immune Globulin Intravenous [human] 10% Liquid) Prescribing Information Boca Raton, FL April 2014

179 Grifols USA Flebogamma 10% DIF (Immune Globulin Intravenous [human] Solution for Intravenous Administration) Prescribing Information Los Angeles, CA January 2016

180 Octapharma USA Octagam (Immune Globulin Intravenous [human] 10% Liquid) Prescribing Information Hoboken, NJ November 2015

181 Baxalta US Inc Hyqvia (Immune Globulin [human] 10% with Recombinant Human Hyaluronidase Solution for Subcutaneous Administration) Prescribing Information Westlake Village, CA April 2016

182 Baxalta US Inc Cuvitru (Immune Globulin Subcutaneous [human] 20% Solution) Prescribing Information Westlake Village, CA September 2016

183 Kedrion Biopharma Gammaked (Immune Globulin Intravenous [human] 10% Caprylate/chromatography Purified) Prescribing Information Fort Lee, NJ September 2016

184 Advisory Committee on Immunization Practices (ACIP) Fiore A.E. Wasley A. Prevention of hepatitis A through active or passive immunization: recommendations of the advisory committee on immunization practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 RR-7 2006 1 23 16708058

185 Centers for Disease Control and Prevention Update: prevention of hepatitis A after exposure to hepatitis A virus and in international travelers. Updated recommendations of the advisory committee on immunization practices (ACIP) MMWR Morb Mortal Wkly Rep 56 2007 1080 1084 17947967

186 Nelson N.P. Updated dosing instructions for immune globulin (human) GamaSTAN S/D for hepatitis a virus prophylaxis MMWR Morb Mortal Wkly Rep 66 2017 959 960 28910270 10.15585/mmwr.mm6636a5 PMC5657912

187 Centers for Disease Control and Prevention CDC Health Information for International Travel 2018 US Department of Health and Human Services Atlanta, GA (Updates may be available at: CDC website)

188 McLean H.Q. Fiebelkorn A.P. Temte J.L. Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 62 RR-04 2013 1 34 23760231

189 Gardulf A. Nocolay U. Asensio O. Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies-a prospective, multi-national study J Clin Immunol 26 2006 177 185 16758340 10.1007/s10875-006-9002-x

190 Nicolay U. Kiessling P. Berger M. Health-related quality of life and treatment satisfaction in north american patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home J Clin Immunol 26 2006 65 72 16418804 10.1007/s10875-006-8905-x

191 Gaspar J. Berritsen B. Jones A. Immunoglobulin replacement treatment by rapid subcutaneous infusion BMJ 79 1998 48 51 10.1136/adc.79.1.48 PMC1717614 9771252

192 Grifols USA Flebogamma 5% DIF (Immune Globulin Intravenous [human] Solution for Intravenous Administration) Prescribing Information Los Angeles, CA April 2015

193 Kurtsberg J. Friedman H.S. Chaffee S. Efficacy of intravenous gamma globulin in autoimmune-mediated pediatric blood dyscrasias Am J Med 83 Suppl 4A 1987 4 9 10.1016/0002-9343(87)90544-4 3118707

194 Lusher J.M. Warrier I. Use of intravenous gamma globulin in children and adolescents with idiopathic thrombocytopenic purpura and other immune thrombocytopenias Am J Med 83 Suppl 4A 1987 10 16 10.1016/0002-9343(87)90545-6 3118703

195 Berkman S.A. Lee M.L. Gale R.P. Clinical uses of intravenous immunoglobulins Ann Intern Med 112 1990 278 292 2404449 10.7326/0003-4819-112-4-278

196 Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia N Engl J Med 319 1988 902 907 2901668 10.1056/NEJM198810063191403

197 Knapp M.J. Colburn P.A. Clinical uses of intravenous immune globulin Clin Pharm 9 1990 509 529 2198124

198 Newburger J.W. Takahashi M. Burns J.C. The treatment of Kawasaki syndrome with intravenous gamma globulin N Engl J Med 315 1986 341 347 2426590 10.1056/NEJM198608073150601

199 Nagashima M. Matsushima M. Matsuoka H. High-dose gammaglobulin therapy for Kawasaki disease J Pediatr 110 1987 710 712 2437278 10.1016/s0022-3476(87)80007-0

200 Newburger J.W. Takahashi M. Gerber M.A. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American heart association Circulation 110 2004 2747 2771 15505111 10.1161/01.CIR.0000145143.19711.78

201 Singh S. Tank N.K. Dwiwedi P. Charan J. Monoclonal antibodies: a review Curr Clin Pharmacol 13 2018 85 99 PMID:28799485 28799485 10.2174/1574884712666170809124728

202 HIGHLIGHTS OF PRESCRIBING INFORMATION: RITUXAN HYCELA (rituximab and hyaluronidase human) injection, for subcutaneous use Initial U.S. Approval: 2017. Revised 6/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761064s000lbl.pdf .

203 Salles G. Barrett M. Robin Foà R. Rituximab in B-cell hematologic malignancies: a review of 20 Years of clinical experience Adv Ther 34 2017 2232 2273 PMID:28983798 28983798 10.1007/s12325-017-0612-x PMC5656728

204 Qi J. Chen S. Chiorazzi N. Rader C. An IgG1-like bispecific antibody targeting CD52 and CD20 for the treatment of B-cell malignancies Methods 154 2019 70 76 Available online 24 August 2018 at https://DOI.org/10.1016/j.ymeth.2018.08.008 30145356 10.1016/j.ymeth.2018.08.008

205 Zhang B. Mini-review: ofatumumab mAbs 1 4 2009 326 331 Previously published online as a mAbs E-publication: http://www.landesbioscience.com/journals/mabs/article/8895 20068404 10.4161/mabs.1.4.8895 PMC2726602

206 McWilliams E.M. Meleb J.M. Cheney C. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia OncoImmunology 5 10 2016 e1226720 (9 pages) Accepted 16 August 2016. Available at: 10.1080/2162402X.2016.1226720 27853650 PMC5087289

207 Robak T. Hellmann A. Kloczko J. Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia Br J Haematol 176 2017 618 628 PMID: 24843434 27977057 10.1111/bjh.14464 PMC5324531

208 Segal N.H. Logan T.F. Hodi S. Results from an integrated safety analysis of urelumab, an agonist anti-CD137 monoclonal antibody Clin Cancer Res 23 8 2017 1929 1936 Published OnlineFirst October 18, 2016. Available at: http://clincancerres.aacrjournals.org/content/23/8/1929 27756788 10.1158/1078-0432.CCR-16-1272

209 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Urelumab (CD137 mAb) with rituximab for relapsed, refractory or high-risk untreated chronic lymphocytic leukemia (CLL) patients. Available at: https://clinicaltrials.gov/ct2/show/NCT02420938?term=urelumab&rank=1 .

210 Kashyap M.K. Kumar D. Jones H. Ulocuplumab (BMS-936564/MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway Oncotarget 7 3 January 19, 2016 2809 2822 Published online 2015 Dec 4. PMID:26646452 26646452 10.18632/oncotarget.6465 PMC4823073

211 First in Human Study to Determine the Safety, Tolerability and Preliminary Efficacy of an Anti-CXCR4 Antibody in Subjects With Acute Myelogenous Leukemia and Selected B-cell Cancers. Available at: https://clinicaltrials.gov/ct2/show/NCT01120457?term=ulocuplumab&rank=5 .

212 Lin T.S. Stock W. Xu H. A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia Leuk Lymphoma 50 12 2009 1958 1963 PMID: 19860603 19860603 10.3109/10428190903186486 PMC8166408

213 de Vos S. Forero-Torres A. Ansell S.M. A phase II study of dacetuzumab (SGN-40) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) and correlative analyses of patient-specific factors J Hematol Oncol 7 2014 44 PMID:24919462 24919462 10.1186/1756-8722-7-44 PMC4065310

214 Fayad L. Ansell S.M. Advani R. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial Leuk Lymphoma 56 9 2015 2569 2578 PMID:25651427 25651427 10.3109/10428194.2015.1007504

215 Awan F.T. Hillmen P. Hellmann A. A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia Br J Haematol 167 2014 466 477 PMID:25130401 25130401 10.1111/bjh.13061

216 Kovtun Y. Jones G.E. Adams S. A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells Blood Adv 2 8 April 24, 2018 848 858 PMID:29661755 29661755 10.1182/bloodadvances.2018017517 PMC5916008

217 Aigner M. Feulner J. Schaffer S. T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct Leukemia 27 5 April 2013 1107 1115 Epub 2012 Nov 26. PMID:23178753 23178753 10.1038/leu.2012.341

218 Xie L.H. Biondo M. Busfield S.J. CD123 target validation and preclinical evaluation of ADCC activity of anti-CD123 antibody CSL362 in combination with NKs from AML patients in remission Blood Canc J 7 2017 e567 published online 2 June 2017. PMID:28574487. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520399/ 10.1038/bcj.2017.52 PMC5520399 28574487

219 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Study of Biomarker-Based Treatment of Acute Myeloid Leukemia. Available at: https://clinicaltrials.gov/ct2/show/NCT03013998?term=samalizumab&rank=3 .

220 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Ficlatuzumab With High Dose Cytarabine in Relapsed and Refractory AML available at: https://clinicaltrials.gov/ct2/show/NCT02109627?term=Ficlatuzumab&rank=3 .

221 Egan P.C. Reagan J.L. The return of gemtuzumab ozogamicin: a humanized anti-CD33 monoclonal antibody–drug conjugate for the treatment of newly diagnosed acute myeloid leukemia OncoTargets Ther 11 2018 8265 8272 eCollection 2018. PMID:30538495 10.2147/OTT.S150807 PMC6254990 30538495

222 Feldman E.J. Brandwein J. Stone R. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, Lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia J Clin Oncol 23 18 June 20, 2005 4110 4116 PMID: 15961759 15961759 10.1200/JCO.2005.09.133

223 Sekeres M.A. Lancet J.E. Wood B.L. Randomized, phase IIb study of low-dose cytarabine and lintuzumab versus low-dose cytarabine and placebo in older adults with untreated acute myeloid leukemia Haematologica 98 1 January 2013 119 128 Epub 2012 Jul 16. PMID:22801961 22801961 10.3324/haematol.2012.066613 PMC3533673

224 de Weers M. Tai Y.T. van der Veer M.S. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors J Immunol 186 3 2011 1840 1848 Epub 2010 Dec 27. PMID:21187443. Available at: http://www.jimmunol.org/content/186/3/1840 21187443 10.4049/jimmunol.1003032

225 HIGHLIGHTS OF PRESCRIBING INFORMATION DARZALEX (daratumumab) injection. Revised 11/2016 Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf .

226 Shah J.J. Feng L. Thomas S.K. Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial Blood Canc J 6 2016 e396 published online 12 February 2016. PMID:26871714 10.1038/bcj.2016.4 PMC4771967 26871714

227 CENTER FOR DRUG EVALUATION AND RESEARCH; Approval Package for: APPLICATION NUMBER: 125496Orig1s000 Trade Name: Sylvant, Generic Name: siltuximab, Sponsor: Janssen Biotech, Inc, Approval Date: April 23, 2014. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125496Orig1s000Approv.pdf .

228 Le Jeune C. Thomas X. Potential for bispecific T-cell engagers: role of blinatumomab in acute lymphoblastic leukemia Drug Des Dev Ther 10 February 18, 2016 757 765 eCollection 2016. PMID:26937176 10.2147/DDDT.S83848 PMC4762579 26937176

229 Kantarjian H. Stein A. Gökbuget N. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia N Engl J Med 376 9 March 02, 2017 836 847 PMID: 28249141 28249141 10.1056/NEJMoa1609783 PMC5881572

230 HIGHLIGHTS OF PRESCRIBING INFORMATION; BLINCYTO (blinatumomab) for injection, for intravenous use; Initial U.S. Approval: 2014 Revised 7/2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125557s008lbl.pdf .

231 Scott L.J. Brentuximab vedotin: a review in CD30-positive Hodgkin lymphoma Drugs 77 2017 435 445 Published online: 11 February 2017. PMID:28190142 28190142 10.1007/s40265-017-0705-5 PMC7102329

232 Flynn M.J. Zammarchi F. Tyrer P.C. ADCT-301, a pyrrolobenzodiazepine (PBD) dimer–containing antibody–drug conjugate (ADC) Targeting CD25-expressing hematological malignancies Mol Cancer Ther 15 11 November 2016 2709 2721 Epub 2016 Aug 17. PMID:27535974 27535974 10.1158/1535-7163.MCT-16-0233

233 Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02432235?term=Camidanlumab+tesirine&rank=3 .

234 Ansell S.M. Horwitz S.M. Engert A. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's Lymphoma and anaplastic large-cell lymphoma J Clin Oncol 25 2007 2764 2769 PMID:17515574 17515574 10.1200/JCO.2006.07.8972

235 Fanale M. Assouline S. Kuruvilla J. Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma Br J Haematol 164 2 January 2014 258 265 PMID: 24219359 24219359 10.1111/bjh.12630 PMC5308127

236 Pro B. Advani R. Brice P. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma Blood 132 4 July 26, 2018 458 459 PMID:30049735 28974506 10.1182/blood-2017-05-780049 PMC5746164

237 Schmid P. Adams S. Rugo H.S. Atezolizumab and Nab-paclitaxel in advanced triple-negative breast cancer N Engl J Med 379 2018 2108 2121 Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1809615 30345906 10.1056/NEJMoa1809615

238 Adams S. Diamond J.R. Hamilton E. Atezolizumab Plus nab-Paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up a phase 1b clinical trial JAMA Oncol October 19, 2018 [Epub ahead of print]. PMID:30347025 10.1001/jamaoncol.2018.5152 PMC6439843 30347025

239 Cremolini C. Loupakis F. Antoniotti C. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study Lancet Oncol 16 2015 1306 1315 Available at: 10.1016/S1470-2045(15)00122-9 26338525

240 HIGHLIGHTS OF PRESCRIBING INFORMATION; AVASTIN (bevacizumab) injection, for intravenous use; Initial U.S. Approval: 2004 Revised 12/2017; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125085s319lbl.pdf .

241 Inman B.A. Longo T.A. Ramalingam S. Atezolizumab: a PD-L1–blocking antibody for bladder cancer Clin Cancer Res 23 2017 1886 1890 Published OnlineFirst November 30, 2016. PMID:27903674 27903674 10.1158/1078-0432.CCR-16-1417

242 Petrylak D.P. Powles T. Bellmunt J. Atezolizumab (MPDL3280A) monotherapy for patients with metastatic urothelial cancer long-term outcomes from a phase 1 study JAMA Oncol 4 4 April 1, 2018 537 544 PMID:29423515 29423515 10.1001/jamaoncol.2017.5440 PMC5885219

243 Horn L. Spigel D.R. Vokes E.E. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057) J Clin Oncol 35 2017 3924 3933 Available at: DOI: 10.1200/JCO.2017.74.3062 29023213 PMC6075826

244 Hodi F.S. Chiarion-Sileni V. Gonzalez R. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial Lancet Oncol 19 11 2018 1480 1492 Epub 2018 Oct 22. PMID:30361170 30361170 10.1016/S1470-2045(18)30700-9

245 Cella D. Grünwald V. Escudier B. Patient-reported outcomes of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib (CheckMate 214): a randomised, phase 3 trial Lancet Oncol 20 2 February 2019 297 310 Epub 2019 Jan 15. PMID:30658932 30658932 10.1016/S1470-2045(18)30778-2 PMC6701190

246 Coleman R.L. Brady M.F. Herzog T.J. Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial Lancet Oncol 18 6 June 2017 779 791 Epub 2017 Apr 21. PMID:28438473 28438473 10.1016/S1470-2045(17)30279-6 PMC5715461

247 Kaufman H.L. Russell J. Hamid O. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial Lancet Oncol 17 10 October 2016 1374 1385 Epub 2016 Sep 1. PMID:27592805 27592805 10.1016/S1470-2045(16)30364-3 PMC5587154

248 HIGHLIGHTS OF PRESCRIBING INFORMATION; BAVENCIO (avelumab) injection, for intravenous use Initial U.S. Approval: 2017. Revised 3/2017; Available at:: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761049s000lbl.pdf .

249 NIH: National Library of Medicine at Clinicaltrials.gov for 175 Studies found for: Avelumab; Also searched for MSB0010718C and Bavencio. See search details available at: https://clinicaltrials.gov/ct2/results?cond=&term=Avelumab&cntry=&state=&city=&dist= .

250 Ploessl C. Pan A. Maples K.T. Dinutuximab: an anti-GD2 monoclonal antibody for high-risk neuroblastoma Ann Pharmacother 50 5 May 2016 416 422 Epub 2016 Feb 25. PMID:26917818 26917818 10.1177/1060028016632013

251 Dhillon S. Dinutuximab: first global approval Drugs 75 8 May 2015 923 927 PMID:25940913 25940913 10.1007/s40265-015-0399-5

252 Diaz R.J. Ali S. Qadir M.G. The role of bevacizumab in the treatment of glioblastoma J Neuro Oncol 133 3 July 2017 455 467 Epub 2017 May 19. PMID:28527008 10.1007/s11060-017-2477-x 28527008

253 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Anti-LAG-3 Alone & in Combination w/Nivolumab Treating Patients w/Recurrent GBM (Anti-CD137 Arm Closed 10/16/18) Available at: https://www.clinicaltrials.gov/ct2/show/NCT02658981?term=BMS-986016&rank=7 .

254 Lee S.J. Lee S.Y. Lee W.S. Phase I trial and pharmacokinetic study of tanibirumab, a fully human monoclonal antibody to vascular endothelial growth factor receptor 2, in patients with refractory solid tumors Investig New Drugs 35 6 December 2017 782 790 Epub 2017 Apr 8. PMID:28391576 28391576 10.1007/s10637-017-0463-y PMC5694508

255 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Trial to Evaluate the Safety of TTAC-0001(Tanibirumab) in Recurrent Glioblastoma. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03033524?term=tanibirumab&rank=2 .

256 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; TTAC-0001 Phase II Trial With Recurrent Glioblastoma Progressed on Bevacizumab. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03856099?term=ttac-0001&rank=1 .

257 Seimetz D. Lindhofer H. Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM anti-CD3) as a targeted cancer immunotherapy Cancer Treat Rev 36 6 October 2010 458 467 Epub 2010 Mar 27. Review. PMID:20347527 20347527 10.1016/j.ctrv.2010.03.001

258 Seimetz D. Novel monoclonal antibodies for cancer treatment: the trifunctional antibody catumaxomab (Removab) J Cancer 2 2011 309 316 Epub 2011 May 25. PMID:21716847 21716847 10.7150/jca.2.309 PMC3119393

259 Fossati M. Buzzonetti A. Monego G. Immunological changes in the ascites of cancer patients after intraperitoneal administration of the bispecific antibody catumaxomab (anti-EpCAM × anti-CD3) Gynecol Oncol 138 2 August 2015 343 351 Epub 2015 Jun 3. PMID:26049121 26049121 10.1016/j.ygyno.2015.06.003

260 Removab Catumaxomab Product Monograph from Fresnius Biotech. Available at: https://hemonc.org/docs/packageinsert/catumaxomab.pdf .

261 HIGHLIGHTS OF PRESCRIBING INFORMATION: LIBTAYO (cemiplimab-rwlc) injection, for intravenous use Initial U.S. Approval: 09/2018 Last Revised 9/2018 Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761097s000lbl.pdf .

262 Migden M.R. Rischin D. Schmults C.D. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma N Engl J Med 379 4 July 26, 2018 341 351 PMID:29863979 29863979 10.1056/NEJMoa1805131

263 Lee M.J. Parker C.E. Taylor S.R. Efficacy of medical therapies for fistulizing Crohn's disease: systematic review and meta-analysis Clin Gastroenterol Hepatol 16 2018 1879 1892 Available at: 10.1016/j.cgh.2018.01.030 29374617

264 Trigo-Vicente C. Gimeno-Ballester V. García-López S. Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis Int J Clin Pharm 40 2018 1411 1419 Available at: 10.1007/s11096-018-0743-4 30478492

265 HIGHLIGHTS OF PRESCRIBING INFORMATION: HUMIRA (adalimumab) injection, for subcutaneous use. Initial U.S. Approval: 2002 Revised 1/2019. Available at: https://www.rxabbvie.com/pdf/humira.pdf .

266 Hanauer S.B. Sandborn W.J. Rutgeerts P. Human anti–tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial Gastroenterology 130 2 February 2006 323 333 PMID:16472588 16472588 10.1053/j.gastro.2005.11.030

267 Lee S.D. Rubin D.T. Sandborn W.J. Reinduction with certolizumab pegol in patients with Crohn's disease experiencing disease exacerbation: 7-year Data from the PRECiSE 4 study Inflamm Bowel Dis 22 8 August 2016 1870 1880 PMID:27400222 27400222 10.1097/MIB.0000000000000805 PMC4949014

268 Winter T.A. Wright J. Ghosh S. Intravenous CDP870, a PEGylated Fab' fragment of a humanized antitumour necrosis factor antibody, in patients with moderate-to severe Crohn's disease: an exploratory study Aliment Pharmacol Ther 20 11–12 December 2004 1337 1346 PMID:15606396 15606396 10.1111/j.1365-2036.2004.02285.x

269 Sandborn W.J. Lee S.D. Randall C. Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-year results from the PRECiSE 3 study Aliment Pharmacol Ther 40 8 October 2014 903 916 Epub 2014 Aug 22. PMID:25146586 25146586 10.1111/apt.12930

270 Colombel J.F. Sands B.E. Rutgeerts P. The safety of vedolizumab for ulcerative colitis and Crohn's disease Gut 66 5 May 2017 839 851 Epub 2016 Feb 18. PMID:26893500 26893500 10.1136/gutjnl-2015-311079 PMC5531223

271 Rosario M. Dirks N.L. Milch C. A review of the clinical pharmacokinetics, pharmacodynamics, and immunogenicity of vedolizumab Clin Pharmacokinet 56 11 November 2017 1287 1301 Review. PMID:28523450 28523450 10.1007/s40262-017-0546-0 PMC5648740

272 Inokuchi T. Takahashi S. Hiraoka S. Long-term outcomes of patients with Crohn's disease who received infliximab or adalimumab as the first-line biologics J Gastroenterol Hepatol February 6, 2019 [Epub ahead of print]. PMID:30724387 10.1111/jgh.14624 30724387

273 Nelson S.M.L. Nguyen T.M. McDonald J.W.D. Natalizumab for induction of remission in Crohn's disease (Review) Cochrane Database Syst Rev 8 2018 CD006097 PMID:30068022 30068022 10.1002/14651858.CD006097.pub3 PMC6513248

274 HIGHLIGHTS OF PRESCRIBING INFORMATION: TYSABRI (natalizumab) injection, for intravenous use Initial U.S. Approval: 2004 Revised 4/2018. Available at: https://www.tysabri.com/content/dam/commercial/multiple-sclerosis/tysabri/pat/en_us/pdfs/tysabri_prescribing_information.pdf .

275 Lebwohl M. Strober B. Menter A. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis N Engl J Med 373 14 October 2015 1318 1328 PMID:26422722 26422722 10.1056/NEJMoa1503824

276 HIGHLIGHTS OF PRESCRIBING INFORMATION: SILIQ (brodalumab) injection, for subcutaneous use. Initial U.S. Approval: 2017 Revised 2/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761032lbl.pdf .

277 Blair H.A. Deeks E.D. Abatacept: a review in rheumatoid arthritis Drugs 77 11 July 2017 1221 1233 PMID:28608166 28608166 10.1007/s40265-017-0775-4

278 Goldzweig O. Hashkes P.J. Abatacept in the treatment of polyarticular JIA: development, clinical utility, and place in therapy Drug Des Dev Ther 5 January 26, 2011 61 70 PMID:21340039 10.2147/DDDT.S16489 PMC3038996 21340039

279 HIGHLIGHTS OF PRESCRIBING INFORMATION: ORENCIA (abatacept) for injection for intravenous use injection, for subcutaneous use. Initial U.S. Approval: 2005 Revised 12/2013. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125118s171lbl.pdf .

280 Ruiz Garcia V. Burls A. Cabello J.B. Certolizumab pegol (CDP870) for rheumatoid arthritis in adults (Review) Cochrane Database Syst Rev 9 2017 CD007649 PMID:28884785 28884785 10.1002/14651858.CD007649.pub4 PMC6483724

281 Navarra S.V. Guzmán R.M. Gallacher A.E. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial Lancet 377 2011 721 731 Epub 2011 Feb 4. PMID:21296403 21296403 10.1016/S0140-6736(10)61354-2

282 Chao Y.S. Adcock L. CADTH RAPID RESPONSE REPORT: Belimumab Treatment for Adults with Systemic Lupus Erythematosus: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines May 2018 CADTH Ottawa (CADTH rapid response report: summary with critical appraisal). Publication Date: May 23, 2018. Available at: https://www.cadth.ca/sites/default/files/pdf/htis/2018/RC0989%20Benlysta%20for%20Lupus%20Final.pdf 30379511

283 Sciascia S. Radin M. Yazdany J. Efficacy of belimumab on renal outcomes in patients with systemic lupus erythematosus: a systematic review Autoimmun Rev 16 3 March 2017 287 293 Epub 2017 Jan 29. PMID:28147262 28147262 10.1016/j.autrev.2017.01.010

284 Usta C. Turgut N.T. Bedel A. How abciximab might be clinically useful Int J Cardiol 222 November 1, 2016 1074 1078 Epub 2016 Aug 4. Review. PMID:27519521 27519521 10.1016/j.ijcard.2016.07.213

285 Hovingh G.K. Guyton J.R. Langslet G. Alirocumab dosing patterns during 40 months of open-label treatment in patients with heterozygous familial hypercholesterolemia J Clin Lipidol 12 6 2018 Nov - Dec 1463 1470 Epub 2018 Aug 30. PMID:30287210 30287210 10.1016/j.jacl.2018.08.011

286 Shahawy M.E. Cannon C.P. Blom D.J. Efficacy and safety of alirocumab versus ezetimibe over 2 years (from ODYSSEY COMBO II) Am J Cardiol 120 6 September 15, 2017 931 939 Epub 2017 Jun 28. PMID:28750828 28750828 10.1016/j.amjcard.2017.06.023

287 HIGHLIGHTS OF PRESCRIBING INFORMATION: PRALUENT (alirocumab) injection, for subcutaneous use. Initial U.S. Approval: 2015. Revised: 12/2018. Available at: http://products.sanofi.us/praluent/praluent.pdf .

288 Sabatine M.S. Giugliano R.P. Keech A.C. Evolocumab and clinical outcomes in patients with cardiovascular disease N Engl J Med 376 2017 1713 1722 PMID: 28304224 28304224 10.1056/NEJMoa1615664

289 HIGHLIGHTS OF PRESCRIBING INFORMATION: REPATHA (evolocumab) injection, for subcutaneous use. Initial U.S. Approval: 2015 Revised 12/2017. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125522s013lbl.pdf .

290 Kastelein J.J.P. Nissen S.E. Rader D.J. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study Eur Heart J 37 17 May 1, 2016 1360 1369 Epub 2016 Jan 12. PMID:26757788 26757788 10.1093/eurheartj/ehv707 PMC4852062

291 Ridker P.M. Rose L.M. Kastelein J.J.P. Cardiovascular event reduction with PCSK9 inhibition among 1578 patients with familial hypercholesterolemia: results from the SPIRE randomized trials of bococizumab J Clin Lipidol 12 4 2018 Jul - Aug 958 965 Epub 2018 Apr 3. PMID:29685591 29685591 10.1016/j.jacl.2018.03.088

292 Coles A.J. Cohen J.A. Fox E.J. Alemtuzumab CARE-MS II 5-year follow-up: efficacy and safety findings Neurology 89 11 September 12, 2017 1117 1126 Epub 2017 Aug 23. PMID:28835403 28835403 10.1212/WNL.0000000000004354 PMC5595276

293 Montalban X. Hauser S.L. Kappos L. Ocrelizumab versus placebo in primary progressive multiple sclerosis N Engl J Med 376 3 January 19, 2017 209 220 PMID:28002688 28002688 10.1056/NEJMoa1606468

294 Voortman M.M. Greiner P. Moser D. The effect of disease modifying therapies on CD62L expression in multiple sclerosis Mult Scler J Exp Transl Clin 4 3 September 20, 2018 2055217318800810. PMID:30263146 10.1177/2055217318800810 PMC6149021 30263146

295 HIGHLIGHTS OF PRESCRIBING INFORMATION: TYSABRI (natalizumab) injection, for intravenous use. Initial U.S. Approval: 2004. Revised on 1/2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125104s0576lbl.pdf .

296 Guo X. Higgs B.W. Bay-Jensen A.C. Suppression of T cell activation and collagen accumulation by an anti-FNAR1 mAb, Anifrolumab, in adult patients with systemic sclerosis J Investig Dermatol 135 10 October 2015 2402 2409 Epub 2015 May 20. PMID:25993119 25993119 10.1038/jid.2015.188

297 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; A study to assess the safety and efficacy of elezanumab when added to standard of care in relapsing forms of multiple sclerosis. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03737851?term=elezanumab&rank=1 .

298 Agius M.A. Klodowska-Duda G. Maciejowski M. Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study Mult Scler 25 2 February 2019 235 245 Epub 2017 Nov 16. PMID:29143550 29143550 10.1177/1352458517740641 PMC6360486

299 Constantinescu C.S. Asher A. Fryze W. Randomized phase 1b trial of MOR103, a human antibody to GM-CSF, in multiple sclerosis Neurol Neuroimmunol Neuroinflamm 2 4 May 21, 2015 e117 eCollection 2015 Aug. PMID:26185773 26185773 10.1212/NXI.0000000000000117 PMC4442097

300 NIH: National Library of Medicine at Clinicaltrialsgov Clinical trial; A Phase 3, Randomized, Multi-center, Double-blinded, Active-controlled Study to Assess the Efficacy and Safety/Tolerability of Ublituximab (TG-1101; UTX) as Compared to Teriflunomide in Subjects With Relapsing Multiple Sclerosis (RMS) (ULTIMATE 1). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03277261?term=ublituximab&rank=3 .

301 Connick P. De Angelis F. Parker R.A. Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MSSMART): a multi-arm phase IIb randomised, double-blind, placebo controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis BMJ Open 8 8 August 30, 2018 e021944 PMID:30166303 10.1136/bmjopen-2018-021944 PMC6119433 30166303

302 Cadavid D. Balcer L. Galetta S. Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial Lancet Neurol 16 3 March 2017 189 199 Epub 2017 Feb 15. PMID:28229892 28229892 10.1016/S1474-4422(16)30377-5

303 Bleecker E.R. FitzGerald J.M. Chanez P. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial Lancet 388 10056 October 29, 2016 2115 2127 Epub 2016 Sep 5. PMID:27609408 27609408 10.1016/S0140-6736(16)31324-1

304 HIGHLIGHTS OF PRESCRIBING INFORMATION: DUPIXENT (dupilumab) injection, for subcutaneous use Initial U.S. Approval: 2017 Last revised: 3/2017.Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761055lbl.pdf .

305 Duggan S. Caplacizumab: first global approval Drugs 78 15 October 2018 1639 1642 Erratum in: Drugs. 2018 Dec;78 (18): 1955. PMID:30298461 30298461 10.1007/s40265-018-0989-0 PMC6280848

306 Peyvandi F. Scully M. Hovinga J.A.K. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura J Thromb Haemost 15 7 July 2017 1448 1452 Epub 2017 Jun 5. PMID:28445600 28445600 10.1111/jth.13716

307 Peyvandi F. Scully M. Hovinga J.A.K. Caplacizumab for acquired thrombotic thrombocytopenic purpura N Engl J Med 374 6 February 11, 2016 511 522 PMID:26863353 26863353 10.1056/NEJMoa1505533

308 Scully M. Cataland S.R. Peyvandi F. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura N Engl J Med 380 4 January 24, 2019 335 346 Epub 2019 Jan 9. PMID:30625070 30625070 10.1056/NEJMoa1806311

309 Ataga K.I. Kutlar A. Kanter J. Crizanlizumab for the prevention of pain crises in sickle cell disease N Engl J Med 376 5 February 2, 2017 429 439 Epub 2016 Dec 3. PMID:27959701 27959701 10.1056/NEJMoa1611770 PMC5481200

310 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients. Available at: https://clinicaltrials.gov/ct2/show/NCT03474965?term=crizanlizumab&rank=1 .

311 Johnson S. Gerding D.N. Bezlotoxumab Clin Infect Dis 68 4 February 1, 2019 699 704 PMID:30020417 30020417 10.1093/cid/ciy577

312 Navalkele B.D. Chopra T. Bezlotoxumab: an emerging monoclonal antibody therapy for prevention of recurrent Clostridium difficile infection Biologics 12 January 18, 2018 11 21 eCollection 2018. Review. PMID:29403263 29403263 10.2147/BTT.S127099 PMC5779312

313 Simões E.A.F. Bont L. Manzoni P. Past, present and future approaches to the prevention and treatment of respiratory syncytial virus infection in children Infect Dis Ther 7 1 March 2018 87 120 Epub 2018 Feb 22. Review. PMID:29470837 29470837 10.1007/s40121-018-0188-z PMC5840107

314 Tripp R.A. Power U.F. Openshaw P.J.M. Respiratory syncytial virus: targeting the G protein provides a new approach for an old problem J Virol 92 3 January 17, 2018 e01302 e01317 Print 2018 Feb 1. PMID:29118126 29118126 10.1128/JVI.01302-17 PMC5774885

315 NIH: National Library of Medicine at Clinicaltrials.gov Clinical trial; 155 Studies found for: basiliximab. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=basiliximab&cntry=&state=&city=&dist= .

316 Sun Z.J. Du X. Su L.L. Efficacy and safety of basiliximab versus daclizumab in kidney transplantation: a meta-analysis Transplant Proc 47 8 October 2015 2439 2445 PMID: 26518947 26518947 10.1016/j.transproceed.2015.08.009

317 Rostainga L. Salibab F. Calmusc Y. Review article: use of induction therapy in liver transplantation Transplant Rev 26 4 October 2012 246 260 Epub 2012 Aug 3. Review. PMID:22863028 10.1016/j.trre.2012.06.002 22863028

318 Kittipibul V. Tantrachoti P. Ongcharit P. Low- dose basiliximab induction therapy in heart transplantation Clin Transplant 31 12 December 2017 Epub 2017 Nov 3. PMID:28990220 10.1111/ctr.13132 28990220

319 Butts R.J. Dipchand A.I. Sutcliffe D. Comparison of basiliximab vs antithymocyte globulin for induction in pediatric heart transplant recipients: an analysis of the International Society for Heart and Lung Transplantation database Pediatr Transplant 22 4 June 2018 e13190 PMID:29878688 29878688 10.1111/petr.13190

320 Kutilek S. Burosumab: a new drug to treat hypophosphatemic rickets Sudan J Paediatr 17 2 2017 71 73 PMID:29545670 29545670 10.24911/SJP.2017.2.11 PMC5845463

321 Insogna K.L. Briot K. Imel E.A. A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of burosumab, an anti-FGF23 antibody, in adults with X-linked hypophosphatemia: week 24 primary analysis J Bone Miner Res 33 8 August 2018 1383 1393 Epub 2018 Jun 26. PMID:29947083 29947083 10.1002/jbmr.3475

322 Cummings S.R. San Martin J M.D. McClung M.R. Denosumab for prevention of fractures in postmenopausal women with osteoporosis N Engl J Med 361 8 August 20, 2009 756 765 Epub 2009 Aug 11. Erratum in: N Engl J Med. 2009 Nov 5; 361(19): 1914. PMID:19671655 19671655 10.1056/NEJMoa0809493

323 Zaheer S. LeBoff M. Lewiecki E.M. Denosumab for the treatment of osteoporosis Expert Opin Drug Metabol Toxicol 11 3 March 2015 461 470 Epub 2015 Jan 22. PMID:25614274 10.1517/17425255.2015.1000860 PMC4480604 25614274

324 Deeks E.D. Denosumab: a review in postmenopausal osteoporosis Drugs Aging 35 2 February 2018 163 173 Review. Erratum in: Drugs Aging. 2018 Mar 9. PMID:29435849 29435849 10.1007/s40266-018-0525-7

325 Gül G. Sendur M.A.N. Aksoy S. A comprehensive review of denosumab for bone metastasis in patients with solid tumors Curr Med Res Opin 32 1 2016 133 145 Epub 2015 Nov 25. Review. PMID:26451465 26451465 10.1185/03007995.2015.1105795

326 Raje N. Terpos E. Willenbacher W. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study Lancet Oncol 19 3 March 2018 370 381 Epub 2018 Feb 9. PMID:29429912 29429912 10.1016/S1470-2045(18)30072-X

327 Dugel P.U. Jaffe G.J. Sallstig P. Brolucizumab versus Aflibercept in participants with neovascular age-related macular degeneration: a randomized trial Ophthalmology 124 9 September 2017 1296 1304 Epub 2017 May 24. PMID:28551167 28551167 10.1016/j.ophtha.2017.03.057

328 HIGHLIGHTS OF PRESCRIBING INFORMATION: ILARIS (canakinumab) injection, for subcutaneous use. Initial U.S. Approval: 2009. Last revised 12/2016. Available at: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/ilaris.pdf .

329 Katoh M. Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β-catenin signaling activation (Review) Int J Mol Med 42 2 August 2018 713 725 Epub 2018 May 17. PMID:29786110 29786110 10.3892/ijmm.2018.3689 PMC6034925

330 KATOH M. Katoh M. Molecular genetics and targeted therapy of WNT-related human diseases (Review) Int J Mol Med 40 3 September 2017 587 606 Epub 2017 Jul 19. PMID:28731148 28731148 10.3892/ijmm.2017.3071 PMC5547940

331 Department of Health and Human Services Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for Industry. Revised Preventive Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jacob Disease (CJD) and Variant Creutzfeldt-Jacob Disease (vCJD) by Blood and Blood Products January 2002 From the US Food and Drug Administration (FDA) website

Further reading

1 Centers for Disease Control Immunization Practices Advisory Committee (ACIP) Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures MMWR Recomm Rep (Morb Mortal Wkly Rep) 40 RR-10 1991 1 28 1865873

2 Centers for Disease Control Update on adult immunization: recommendations of the immunization practices advisory committee (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 40 RR-12 1991 18,49,70,87 1956371

3 Kretsinger K. Broder K.R. Cortese M.M. Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 2006 1 37 17167397

4 Broder K.R. Cortese M.M. Iskander J.K. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep (Morb Mortal Wkly Rep) 55 2006 1 34 16557217

5 Snydman D.R. Werner B.G. Dougherty N.N. Cytomegalovirus immune globulin prophylaxis in liver transplantation: a randomized, double-blind, placebo-controlled trial Ann Intern Med 119 1993 984 991 8214995 10.7326/0003-4819-119-10-199311150-00004

6 Bowden R.A. Sayers M. Flournoy N. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation N Engl J Med 314 1986 1006 1010 3007984 10.1056/NEJM198604173141602

7 Mair-Jenkins J. Saavedra-Campos M. Baillie J.K. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis J Infect Dis 211 2015 80 90 25030060 10.1093/infdis/jiu396 PMC4264590

8 US Food and Drug Administration Guidance for Industry Influenza: Developing Drugs for Treatment And/or Prophylaxis 2011 US Food and Drug Administration Silver Spring, MD

9 Ohmit S.E. Petrie J.G. Cross R.T. Johnson E. Monto A.S. Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection J Infect Dis 204 2011 1879 1885 21998477 10.1093/infdis/jir661

10 Arnon S.S. Schechter R. Inglesby T.V. for the Working Group on Civilian Biodefense. Botulinum toxin as a biologic weapon: medical and public health management J Am Med Assoc 285 2001 1059 1070 10.1001/jama.285.8.1059 11209178