B-cell maturation antigen–Cluster of differentiation 3 complex (BCMA–CD3)

The BCMA–CD3 protein–protein interface is a pharmacologically induced target created by bispecific antibodies that bridge B-cell maturation antigen (BCMA) on plasma cells and the CD3 epsilon subunit of the T-cell receptor complex (Moreau et al., 2022, NEJM). BCMA, also known as TNFRSF17, is a cell surface receptor essential for the survival of long-lived plasma cells and is highly overexpressed in multiple myeloma (Cho et al., 2020, Frontiers in Immunology). CD3 is a co-receptor involved in activating both cytotoxic T cells and T helper cells. By simultaneously binding both proteins, bispecific T-cell engagers (BiTEs) or bispecific antibodies facilitate the formation of an artificial immune synapse, bypassing the need for traditional major histocompatibility complex (MHC) recognition (Lesokhin et al., 2023, Nature Medicine). This interaction triggers T-cell activation, the release of perforins and granzymes, and the subsequent lysis of the BCMA-positive malignant cells. This therapeutic strategy is primarily utilized in the treatment of relapsed or refractory multiple myeloma, where it has shown significant clinical efficacy in patients who have exhausted other lines of therapy (Dhillon, 2022, Drugs).

Other names

TNFRSF17–CD3 complexBCMA–CD3 epsilon interfaceBCMA–CD3 bispecific targetB-cell maturation antigen–T-cell receptor complex interface

Bispecific T-cell engagement leading to redirected T-cell mediated cytotoxicity against BCMA-expressing cells.