NKp46/CD16-based BCMA-targeted NK cell engager SAR445514

An engineered tri-specific natural killer (NK) cell engager (NKCE) containing specific antibodies targeting the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), and the NK activating receptors natural cytotoxicity triggering receptor (NKp46; activating natural killer receptor p46) and CD16, with potential immunostimulating and antineoplastic activities. Upon administration of NKp46/CD16-based BCMA-targeted NK cell engager SAR445514, the NKCE targets and binds to BCMA expressed on tumor cells and simultaneously binds, via the activating receptors NKp46 and CD16, to NK cells, thereby bringing BCMA-expressing tumor cells and NK cells together. This stimulates the NK cells and results in the selective NK cell-mediated tumor cell lysis of BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a member of the tumor necrosis factor receptor superfamily (TNFRSF) that binds to both a proliferation-inducing ligand (APRIL; TNFSF13) and B-cell activating factor (BAFF; TNFSF13B), plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.