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Myeloma-associated antigens are a diverse group of proteins overexpressed on the surface of malignant plasma cells in multiple myeloma, serving as critical targets for modern immunotherapy [PubMed: 33461568]. Key antigens include CD38, SLAMF7, B-cell maturation antigen (BCMA), and GPRC5D, each contributing to the survival and proliferation of myeloma cells within the bone marrow microenvironment [PubMed: 32690320, 35947488]. These targets have enabled the development of various therapeutic modalities, such as monoclonal antibodies (e.g., daratumumab), bispecific T-cell engagers (e.g., teclistamab), and CAR-T cell therapies (e.g., idecabtagene vicleucel) [PubMed: 29147051, 33461568]. While these therapies have significantly improved clinical outcomes, challenges such as antigen loss, heterogeneous expression, and severe side effects like cytokine release syndrome remain prominent [PubMed: 32690320]. Understanding the specific biology and expression patterns of these antigens is essential for personalizing treatment and overcoming resistance mechanisms in patients with relapsed or refractory disease [PubMed: 33461568].
Therapeutic agents targeting these antigens work through several mechanisms: monoclonal antibodies induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP); antibody-drug conjugates (ADCs) deliver cytotoxic agents directly to the cell; and bispecific antibodies and CAR-T cells redirect or engineer T-cells to recognize and kill the antigen-expressing plasma cells [PubMed: 33461568, 32690320].
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