B-cell maturation antigen (BCMA) and Cluster of differentiation 3 epsilon (CD3E) complex (BCMA-CD3)

The BCMA–CD3 cell-surface interface is a synthetic therapeutic target created by bispecific antibodies that bridge B-cell maturation antigen (BCMA) on malignant plasma cells and the CD3 epsilon subunit on T-lymphocytes. BCMA, also known as TNFRSF17, is a member of the tumor necrosis factor receptor superfamily that is highly and selectively expressed on the surface of late-stage B cells and plasma cells, where it promotes cell survival and proliferation (UniProt Q02223). CD3 is a multi-subunit protein complex that acts as a T-cell co-receptor, essential for signal transduction following T-cell receptor engagement (UniProt P04234). By simultaneously binding both molecules, bispecific T-cell engagers (TCEs) facilitate the formation of an artificial immunological synapse, bypassing the requirement for traditional major histocompatibility complex (MHC) class I recognition. This interaction leads to the localized activation of T-cells, resulting in the release of cytotoxic granules such as perforin and granzymes, which induce apoptosis in the BCMA-expressing tumor cells. This target is central to modern immunotherapy strategies for relapsed or refractory multiple myeloma, with approved drugs like teclistamab and elranatamab demonstrating significant clinical efficacy (FDA 2022, 2023). However, the potent immune activation can lead to serious adverse events, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Other names

BCMA-CD3TNFRSF17-CD3EBCMA x CD3B-cell maturation antigen-CD3 epsilon interface

Bispecific T-cell engagement leading to redirected T-cell mediated lysis of BCMA-expressing cells.