IDP-023 + isatuximab + interleukin-2

IDP-023 + isatuximab + interleukin-2 is an investigational combination therapy composed of three agents: - **IDP-023:** An allogeneic, off-the-shelf cell therapy consisting of cytomegalovirus-exposed, FcεR1γ-deficient natural killer (g-NK) cells. These cells possess both innate and adaptive-like immune mechanisms, including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC), and targeting of HLA-E expressing cells via NKG2C receptors. IDP-023 can also clear potential Epstein-Barr virus reservoirs and is being developed as a novel immunotherapy for multiple sclerosis and hematological cancers[1][3][5]. - **Isatuximab:** A monoclonal antibody targeting CD38, broadly expressed on malignant plasma cells and other immune cells. Isatuximab induces tumor cell death through ADCC, complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and direct apoptosis via CD38 inhibition. Isatuximab is FDA-approved for multiple myeloma and has orphan drug designation[2][4][6]. - **Interleukin-2 (IL-2):** A cytokine used to stimulate proliferation, survival, and activity of NK cells and T cells, likely included here to enhance expansion and persistence of IDP-023 g-NK cells in vivo. This combination is being evaluated for safety, tolerability, and biologic activity, primarily in patients with progressive forms of multiple sclerosis. Clinical studies combine these agents (often also with ocrelizumab) to target autoreactive immune cells and modulate disease progression[3].