CS1 (SLAMF7), a pivotal immune receptor, plays a dual role in modulating immune responses in autoimmune diseases and cancer. In autoimmunity, aberrant CS1 signaling contributes to the activation of autoreactive lymphocytes, driving pathologies such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conversely, in oncology, CS1 serves as a promising immunotherapeutic target, exemplified by the efficacy of the monoclonal antibody Elotuzumab in multiple myeloma. CS1 mediates immune cell functions through intricate signaling pathways, including interactions with EAT-2 and SAP adaptors, which influence cytotoxicity, cytokine production, and immune homeostasis. Beyond cancer and autoimmune diseases, soluble and membrane-bound forms of CS1 are emerging as biomarkers and potential therapeutic targets. Despite significant progress, gaps remain in understanding CS1\u2019s mechanisms, variability in expression, and role in other diseases. This study explores the multifaceted functions of CS1, proposing innovative strategies to leverage its therapeutic potential across diverse pathologies.
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The Multifaceted Role of CS1 (SLAMF7) in Immunoregulation: Implications for Cancer Therapy and Autoimmune Disorders.
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Central Labs, King Khalid University, AlQura'a, Abha, Saudi Arabia; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. Electronic address:
CS1 (SLAMF7), a pivotal immune receptor, plays a dual role in modulating immune responses in autoimmune diseases and cancer. In autoimmunity, aberrant CS1 signaling contributes to the activation of autoreactive lymphocytes, driving pathologies such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conversely, in oncology, CS1 serves as a promising immunotherapeutic target, exemplified by the efficacy of the monoclonal antibody Elotuzumab in multiple myeloma.
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Department of Hematology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands
Background: Autologous BCMA-specific CAR T-cell therapies have substantial activity in multiple myeloma (MM). However, due to logistical limitations and BCMA relapses, there is a need for alternatives. UCARTCS1 cells are 'off-the-shelf' allogeneic CAR T-cells derived from healthy donors targeting SLAMF7 (CS1), which is highly expressed in MM cells.
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Laboratory of Molecular Imaging and Therapy (MITH), Department of Biomedical Sciences, Vrije Universiteit Brussel, Brussels, Belgium.
Introduction: Multiple myeloma (MM) remains incurable, despite the advent of chimeric antigen receptor (CAR)-T cell therapy. This unfulfilled potential can be attributed to two untackled issues: the lack of suitable CAR targets and formats. In relation to the former, the target should be highly expressed and reluctant to shedding; two characteristics that are attributed to the CS1-antigen.
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INSERM, Human Immunology, Pathophysiology, Immunotherapy (HIPI), Institut de Recherche Saint-Louis, Université de Paris-Cité, Paris, France.
Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting multiple myeloma cells using CAR T-cell therapy are needed. SLAMF7 (also known as CS1) and CD38 on tumor plasma cells represent potential alternative targets for CAR T-cell therapy in multiple myeloma, but their expression on activated T cells and other hematopoietic cells raises concerns about the efficacy and safety of such treatments.
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Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM.
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