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

The BCMA–CD3 cellular interface is a therapeutic target configuration created by bispecific antibodies that bridge B-cell maturation antigen (BCMA) on target cells and the CD3 receptor on T-cells (UniProt Q02223; UniProt P07766). BCMA, a member of the tumor necrosis factor receptor superfamily (TNFRSF17), is essential for the survival of long-lived plasma cells and is highly expressed in multiple myeloma (PubMed: 32694743). CD3 is a multi-protein complex that acts as a T-cell co-receptor, crucial for signal transduction following antigen recognition. When a bispecific agent binds both BCMA and CD3, it facilitates the formation of a synthetic immunological synapse between a cytotoxic T-cell and a BCMA-positive plasma cell. This proximity-induced engagement triggers T-cell activation and the secretion of cytotoxic granules, such as perforin and granzymes, leading to the lysis of the target cell (PubMed: 36223505). This mechanism is independent of major histocompatibility complex (MHC) class I expression, allowing T-cells to effectively eliminate tumor cells that might otherwise evade immune detection. Clinically, targeting this interface has proven highly effective in treating relapsed or refractory multiple myeloma, with several approved therapies like teclistamab and elranatamab now available (FDA.gov). However, the potent activation of T-cells can lead to systemic inflammatory responses, most notably cytokine release syndrome (CRS) and neurotoxicity (PubMed: 30635431).

Other names

TNFRSF17-CD3CD269-CD3BCMA-CD3 cellular interfaceBCMA-CD3 bispecific target

Bispecific T-cell redirection and activation leading to MHC-independent cytotoxicity