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Antibody-Drug Conjugates for Multiple Myeloma: Just the Beginning, or the Beginning of the End?

Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen

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… Clinical trials with blocked ricin immunotoxins. Curr. Top. Microbiol. Immunol. 1998;234:35–56. doi: 10.1007/978-3-642-72153-3_3. 27. Grossbard M.L., Fidias P., Kinsella J., O’Toole J., Lambert J.M., Blattler W.A., Esseltine D., Braman G., Nadler L.M., Anderson K.C. … Anti-B4-blocked ricin: A phase II trial of 7 day continuous infusion in patients with multiple myeloma. Br. J. Haematol. 1998;102:509–515. doi: 10.1046/j.1365-2141.1998.00799.x. 28. Yu B., Jiang T., Liu D. BCMA-targeted immunotherapy for multiple myeloma. J. Hematol. …

LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.

Lysosomal-associated protein transmembrane (LAPTM) family members-LAPTM4A, LAPTM4B, and LAPTM5-regulate lysosomal integrity, autophagy-lysosome flux, lipid homeostasis, and immune signaling, pathways increasingly implicated in neurological disease. This review synthesizes structure-function evidence for LAPTM proteins and examines how their dysregulation contributes to Alzheimer's and Parkinson's disease, ischemia-reperfusion injury, and gliomas. Based on a targeted narrative analysis of primary and translational studies, we highlight that LAPTM proteins influence lysosomal acidification and m

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… Additionally, it confers resistance to toxins (e.g., Shiga toxin, ricin) through endosomal processing and ceramide-mediated membrane stabilization [ 20 ]. … Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation. PLoS Biology. 2018;16(11):e2006951. doi: 10.1371/journal.pbio.2006951. https://doi.org/10.1371/journal.pbio.2006951. 21. Ding Y, Jiang Y, Zeng H, Zhou M, Zhou X, Yu Z, et al. …

Production of IL-1β by bone marrow-derived macrophages in response to chemotherapeutic drugs: synergistic effects of doxorubicin and vincristine.

Cytotoxic chemotherapeutic drugs, especially when used in combination, are widely employed to treat a variety of cancers in patients but often lead to serious symptoms that negatively affect physical functioning and quality of life. There is compelling evidence that implicates cytotoxic chemotherapy-induced inflammation in the etiology of these symptoms. Because IL-1β plays a central role as an initiator cytokine in immune responses, we compared doxorubicin, a drug known to induce IL-1β production, with ten other commonly prescribed chemotherapeutic drugs in their ability to lead to processing

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… X Tiwari AK Hopper-Borge E Ouyang J Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10) PLoS One 2009 4 e7520 10.1371/journal.pone.0007520 19841739 PMC2759525 56 Korcheva V Wong J Corless C Iordanov M Magun B Administration of ricin …

Antibody-based therapies in multiple myeloma.

The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic r

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… However, early studies using anti-CD38 mAb with or without an immunotoxin (ricin) have not led to useful clinical applications [ 4 , 40 ]. Recently, a human anti-CD38 IgG 1 HuMax-CD38 (Daratumumab) was raised after immunizing transgenic mice (HuMax-Mouse) possessing human, but not mouse, Ig genes. … Anti-CD38-blocked ricin: an immunotoxin for the treatment of multiple myeloma. Blood. 1994;84(9):3017–3025. 41. Tai YT, de Weers M, Li X, et al. Daratumumab, a novel potent human anti-CD38 monoclonal antibody, induces significant killing of human multiple myeloma cells. …

Compartment Syndrome of All Extremities in the Setting of COVID-19-Induced Systemic Capillary Leak Syndrome With Superimposed Myositis.

Three years following the pandemic's emergence, COVID-19 has continued to affect much of the symptomatic population with widely varied respiratory complaints, fevers, numerous unexpected prodromal manifestations, and unknown long-term consequences. Scattered cases involving myopathies, rhabdomyolysis, and compartment syndrome have also been reported throughout the pandemic. Some similar cases have been attributed to systemic capillary leak syndrome (SCLS). Here, we report the development of compartment syndrome involving all extremities in a 57-year-old vaccinated female known to have COVID-19

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… differential diagnosis should be broad, including sepsis, PCV, adrenal insufficiency, amyloidosis, toxic shock syndrome, heart failure, engraftment syndrome, differentiation syndrome, ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, snakebite envenomation, ricin …

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy.

Since the approval of rituximab in 1997, monoclonal antibodies (mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target speci

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… Other payloads which have been investigated in the literature include ricin-like toxins 42 , as these molecules are extremely potent and are believed to have the capacity to induce apoptosis with only a single molecule entering the cytosol. …

Effects of T-Cell Depletion on Allogeneic Hematopoietic Stem Cell Transplantation Outcomes in AML Patients.

Graft versus host disease (GVHD) remains one of the leading causes of morbidity and mortality associated with conventional allogeneic hematopoietic stem cell transplantation (HCT). The use of T-cell depletion significantly reduces this complication. Recent prospective and retrospective data suggest that, in patients with AML in first complete remission, CD34+ selected grafts afford overall and relapse-free survival comparable to those observed in recipients of conventional grafts, while significantly decreasing GVHD. In addition, CD34+ selected grafts allow older patients, and those with medic

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… Donor bone marrow treatment with T101 Fab fragment-ricin A-chain immunotoxin prevents graft- versus -host disease Bone Marrow Transplant. 1989 4 367 371 2789084 24. Filipovich A.H. Vallera D. McGlave P. Polich D. Gajl-Peczalska K. Haake R. Lasky L. Blazar B. Ramsay N.K. Kersey J. …

Immunotherapy targets in pediatric cancer.

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made b

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… Combotox, a 1:1 mixture of anti-CD19 and anti-CD22 antibodies conjugated to deglycosylated ricin-A chain has recently shown hematologic activity in 10/17 children with refractory ALL, of which three were complete responses (Herrera et al., 2009 ). … A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254 . Leuk. Lymphoma 52 , 587 – 596 10.3109/10428194.2010.543714 21275630 PMC3682835 Gaipa G. Basso G. Maglia O. Leoni V. Faini A. Cazzaniga G. Bugarin C. Veltroni M. Michelotto B. …

Human microbiomes in cancer development and therapy.

Colonies formed by bacteria, archaea, fungi, and viral groups and their genomes, metabolites, and expressed proteins constitute complex human microbiomes. An increasing evidences showed that carcinogenesis and disease progression were link to microbiomes. Different organ sources, their microbial species, and their metabolites are different; the mechanisms of carcinogenic or procancerous are also different. Here, we summarize how microbiomes contribute to carcinogenesis and disease progression in cancers of the skin, mouth, esophagus, lung, gastrointestinal, genital, blood, and lymph malignancy

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… As a kinds of phytotoxins vector, bacteria can harbor ricin, saporin, or pseudomonal exotoxins to suppress protein synthesis, induce cancer cells apopotosis. Investigators struggled with regulating microbiome to enhance cancer treatment response and eliminate toxic side effects of cancer therapy. …

Targeted therapy for multiple myeloma: an overview on CD138-based strategies.

Multiple myeloma (MM) is an incurable hematological disease characterized by the uncontrolled growth of plasma cells primarily in the bone marrow. Although its treatment consists of the administration of combined therapy regimens mainly based on immunomodulators and proteosome inhibitors, MM remains incurable, and most patients suffer from relapsed/refractory disease with poor prognosis and survival. The robust results achieved by immunotherapy targeting MM-associated antigens CD38 and CD319 (also known as SLAMF7) have drawn attention to the development of new immune-based strategies and diffe

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… They are mainly derived from bacteria, such as anthrax toxin, Shiga-like toxin, P. aeruginosa exotoxin A and diphtheria toxin, and from plants, such as pokeweed antiviral protein, saporin, ricin and gelonin, and must be engineered to remove the cell-binding domain and replace it with a targeting moiety …

Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review).

Monoclonal antibody technology plays a vital role in biomedical and immunotherapy, which greatly promotes the study of the structure and function of genes and proteins. To date, monoclonal antibodies have gone through four stages: murine monoclonal antibody, chimeric monoclonal antibody, humanised monoclonal antibody and fully human monoclonal antibody; thousands of monoclonal antibodies have been used in the fields of biology and medicine, playing a special role in the pathogenesis, diagnosis and treatment of disease. In this review, we compare the advantages and disadvantages of hybridoma te

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… The main toxins currently used in reagents are diphtheria toxin, abrin, ricin, gelonin, and Pseudomonas aeruginosa endotoxin ( 198 , 207 , 208 ). …

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

Late Breaking Orals.

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Passive Monoclonal and Polyclonal Antibody Therapies

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Targeting Oncoproteins for Molecular Cancer Therapy

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Frontiers in Antibody-Drug Conjugates: Mechanisms, Design Innovations, and Clinical Applications in Targeted Cancer Therapy.

Antibody-drug conjugates (ADCs) represent a transformative class of targeted therapies designed to deliver potent cytotoxic agents specifically to tumor cells, minimizing systemic toxicity. This review provides a comprehensive overview of ADCs, detailing their mechanisms of action, design strategies, and clinical advancements. ADCs utilize monoclonal antibodies to selectively bind tumor-associated antigens, enabling the precise delivery of toxic payloads to cancer cells. The review explores the critical components of ADCs, including the antibody, linker, and payload, and highlights how these e

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… Early constructs, built by chemically coupling murine antibodies to protein toxins like ricin A chain or diphtheria fragments, demonstrated proof-of-principle in vitro. …

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Резюме докладов 2017 Ежегодное совещание Общества общей внутренней медицины.

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