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New developments in the treatment of peripheral T-cell lymphoma - role of Belinostat.

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of rare malignancies that with the exception of anaplastic lymphoma kinase expressing anaplastic large cell lymphoma, share a poor outcome after standard (eg, anthracycline-based) chemotherapy. Most patients are either refractory to initial therapy or eventually relapse. Randomized studies for relapsed/refractory PTCL are not available, however, recently published data show that conventional chemotherapy has very limited efficacy in the salvage setting. Thus, novel drugs are urgently needed to improve the outcome in this settin

FDA-Approved Drugs for Hematological Malignancies-The Last Decade Review.

Hematological malignancies, also referred to as blood cancers, are a group of diseases involving abnormal cell growth and persisting in the blood, lymph nodes, or bone marrow. The development of new targeted therapies including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and, finally, Chimeric Antigen Receptor T (CAR-T) cells has improved the clinical outcomes for blood cancers. In this review, we summarized 52 drugs that were divided into small molecule and macromolecule agents, approved by the Food and Drug

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… Antibody-Drug Conjugates as Anticancer Agents Antibody-drug conjugate (ADC) is an immunoconjugate consisting of an antibody, a highly potent cytotoxic agent (known as the payload), and a chemical linker. … To improve the therapeutic efficacy of mAbs, various modifications have been developed, including currently approved immunoconjugates (five (5) antibody-drug conjugates and one (1) recombinant immunotoxin) and one (1) bispecific monoclonal antibody. …

Antibodies to watch in 2023.

In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevim

Targeted antineoplastic therapy in critically ill cancer patients: a multicenter analysis of the iCHOP registry.

Approximately 20% of intensive care unit (ICU) patients have cancer, and their prognosis has markedly improved in recent years. In addition to improved treatment in the ICU, this is a result of advancements in cancer therapies, including the use of targeted therapies (TTs), such as antibodies and small-molecule kinase inhibitors. Despite the increasing use of TT, there are currently no comprehensive studies examining critically ill cancer patients receiving TT in the ICU. We studied the clinical characteristics of a multicenter cohort of cancer patients who received TT in the ICU. To this end,

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… Fig. 1 Targeted treatment agents applied in the ICU Most TT patients (56%, n = 59) were treated with an antibody, including monoclonal antibodies and immunoconjugates. …

Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogene

Characterization of Belantamab Mafodotin-Induced Corneal Changes in Patients With Multiple Myeloma.

IMPORTANCE: Ocular surface events are a class effect of microtubule-inhibitor payload-containing antibody-drug conjugates (ADCs); the mechanism underlying these events has not been fully elucidated. OBJECTIVE: To characterize corneal epithelial changes in patients with relapsed or refractory multiple myeloma (RRMM) treated with belantamab mafodotin, a maleimidocaproyl monomethyl auristatin-F (MMAF)-containing ADC. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3b case series study was conducted in the US from March 26, 2020, to November 21, 2022, among adults with RRMM. Data were

Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residua

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… Furthermore, it was also reported that some immunoconjugates kill myeloma cells through ADCC or ADCP [ 110 , 111 ]. Importantly, this mechanism of action limits damage of healthy cells and subsequently reduces chemotherapy-associated side effects [ 109 ]. … Targeted Therapy With Immunoconjugates for Multiple Myeloma. Front. Immunol. 2020;11:1155. doi: 10.3389/fimmu.2020.01155. 161. Wang J., Zheng Y., Tu C., Zhang H., Vanderkerken K., Menu E., Liu J. …

Antibodies to watch in 2022.

In this 13th annual installment of the annual 'Antibodies to Watch' article series, we discuss key events in commercial antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. Regulatory review of antibody therapeutics that target the SARS-CoV-2 coronavirus proceeded at an unprecedented pace in 2021, resulting in both emergency use authorizations and full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well as others, in numerous countries. As of November 1, a total of 11 antibody therapeutics had been granted first approvals in either the Un

Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial.

BackgroundMoxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).MethodsEligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and mi

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… Immunoconjugates and new molecular targets in hairy cell leukemia. Hematol Am Soc Hematol Educ Program. 2012;2012:660–666. doi: 10.1182/asheducation.V2012.1.660.3798659. 6. Rosenberg JD, Burian C, Waalen J, et al. …

Therapy of newly diagnosed follicular lymphoma.

Newly diagnosed follicular lymphoma is relatively common and can be effectively treated with several differing approaches. Although the disease is often considered incurable, it is highly responsive to therapy when indicated. This review discusses the indications for treatment, risk stratification systems, treatment options with supporting clinical trial data, and expected therapeutic outcomes in newly diagnosed follicular lymphoma.

89Zr-DFO-Isatuximab for CD38-Targeted ImmunoPET Imaging of Multiple Myeloma and Lymphomas.

Multiple myeloma (MM) is the second most prevalent hematological malignancy. It remains incurable despite the availability of novel therapeutic approaches, marking an urgent need for new agents for noninvasive targeted imaging of MM lesions. CD38 has proven to be an excellent biomarker due to its high expression in aberrant lymphoid and myeloid cells relative to normal cell populations. Using isatuximab (Sanofi), the latest FDA-approved CD38-targeting antibody, we have developed Zirconium-89(89Zr)-labeled isatuximab as a novel immunoPET tracer for the in vivo delineation of MM and evaluated th

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… Purification of the immunoconjugates was performed with a prepacked disposable PD-10 desalting column (GE Healthcare) and concentrated with a 50,000 MWCO Amicon centrifugal filter (Millipore Sigma). Final concentrations were determined with a NanoDrop 2000 spectrometer (Thermo Fisher Scientific). …

Cutaneous Skin Toxicities of Oncological Targeted Therapies: Comprehensive Overview of Mechanisms, Management, and Research Gaps-A Narrative Review.

Targeted therapies in oncology have become a mainstay in therapy of numerous types of cancers. They work by targeting and utilizing (activating, inhibiting, or modulating) molecular pathways that are crucial in pathogenesis of certain cancers and can be divided into numerous classes according to their mechanism. However, since the antigens and molecules they target can take part in homeostasis of the skin and the integument, cutaneous toxicities are a common occurrence. The frequency of certain cutaneous adverse events (CAEs) depends on the causal drug and varies even between drugs of the same

Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

BackgroundGlioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (211At-9E7.4).MethodsWe orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistri

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… Alpha-particle emitting 213Bi-anti-EGFR immunoconjugates eradicate tumor cells independent of oxygenation PLoS One 8 2013 e64730 10.1371/journal.pone.0064730 PMC3665541 23724085 13 Zalutsky M.R. McLendon R.E. Garg P.K. Archer G.E. Schuster J.M. Bigner D.D. … Radioimmunotherapy of neoplastic meningitis in rats using an alpha-particle-emitting immunoconjugate Cancer Res 54 1994 4719 4725 8062270 14 Bäck T. Chouin N. Lindegren S. …

Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies.

Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored

MR imaging findings in some rare neurological complications of paediatric cancer.

Neurological complications of paediatric cancers are a substantial problem. Complications can be primary from central nervous system (CNS) spread or secondary from indirect or remote effects of cancer, as well as cancer treatments such as chemotherapy and radiation therapy. In this review, we present the clinical and imaging findings of rare but important neurological complications in paediatric patients with cancer. Neurological complications are classified into three phases: pre-treatment, treatment and post-remission. Paraneoplastic neurological syndromes, hyperviscosity syndrome, haemophag

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… These lead to thrombosis by inducing cell-cell interactions with platelets, monocytes and endothelium via inflammatory cytokines, tumour antigens, and their immunoconjugates, which promote coagulation activation. …

Antibodies to watch in 2021.

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed an

Paraskeletal and extramedullary plasmacytomas in multiple myeloma at diagnosis and at first relapse: 50-years of experience from an academic institution.

From January 1970 to December 2018, 1304 patients were diagnosed with multiple myeloma (MM) at our institution and 256 (19.6%) had plasmacytomas (Ps) (paraskeletal -PPs- 17.6%, extramedullary -EMPs-1.9%). Patients with Ps had lower serum M-protein and less advanced ISS stage than those without. At first relapse, 192 out of 967 patients (19.8%) developed Ps (PPs 14.6%, EMPs 5.1%). The only factor associated with Ps at relapse was the presence of Ps at diagnosis (46% vs 13%, p < 0.00001) with no impact with exposure to novel drugs or previous autologous stem-cell transplantation (ASCT). The medi

8(th) Annual European Antibody Congress 2012: November 27-28, 2012, Geneva, Switzerland.

The 8th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4th EAC. The new agenda format for 2012 included three parallel tracks on: (1) naked antibodies; (2) antibody drug conjugates (ADCs); and (3) bispecific antibodies and alternative scaffolds. The meeting started and closed with three plenary lectures to give common background and to share the final panel discussion and conclusions. The two day event included case studies and networking for nearly 250 delegates who learned of the latest adva

The Role of Immunotherapy in Multiple Myeloma.

Multiple myeloma is the second most common hematologic malignancy. The treatment of this disease has changed considerably over the last two decades with the introduction to the clinical practice of novel agents such as proteasome inhibitors and immunomodulatory drugs. Basic research efforts towards better understanding of normal and missing immune surveillence in myeloma have led to development of new strategies and therapies that require the engagement of the immune system. Many of these treatments are under clinical development and have already started providing encouraging results. We, for

Naked antibodies and antibody-drug conjugates: targeted therapy for childhood acute lymphoblastic leukemia.

The treatment of childhood acute lymphoblastic leukemia (ALL) has reached overall survival rates exceeding 90%. The present and future challenges are to cure the remainder of patients still dying from disease, and to reduce morbidity and mortality in those who can be cured with standard-of-care chemotherapy by replacing toxic chemotherapy elements while retaining cure rates. With the novel therapeutic options introduced in the last years, including immunotherapies and targeted antibodies, the treatment of ALL is undergoing major changes. For B-cell precursor ALL, blinatumomab, an anti-CD19 bis