daratumumab + isatuximab

Daratumumab + isatuximab is a conceptual combination of two distinct CD38-targeting monoclonal antibodies, each of which binds a different, nonoverlapping epitope on CD38 and exerts antimyeloma effects via immune-mediated and direct cytotoxic mechanisms. Daratumumab is a human IgG1κ monoclonal antibody that induces multiple myeloma cell death primarily through Fc-dependent mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and phagocytosis, and has additional immunomodulatory effects via depletion of CD38-positive regulatory T cells, regulatory B cells, and myeloid-derived suppressor cells, thereby enhancing T‑cell number, clonality, and function.[8][6] Isatuximab is a chimeric/humanized IgG1 monoclonal antibody that binds a distinct CD38 epitope partially encompassing the ectoenzyme catalytic site and can induce direct, caspase-dependent apoptosis of myeloma cells without external cross-linking, as well as Fc-mediated ADCC, ADCP, CDC, and potent inhibition of CD38 ectoenzyme activity, contributing to reversal of adenosine-mediated immunosuppression in the myeloma microenvironment.[2][6] Although both antibodies are individually approved in combination regimens for relapsed/refractory multiple myeloma, their concurrent use together in a single therapeutic regimen is not an established or approved treatment strategy and is primarily of theoretical or experimental interest in the context of CD38 biology and resistance.

Other names

isatuximab-irfcSAR650984SAR-650984SAR 650984