B-cell maturation antigen (BCMA) and T-cell surface glycoprotein CD3 epsilon chain (CD3ε) (BCMA-CD3ε)

BCMA-CD3ε cell-bridging is a therapeutic mechanism of action employed by bispecific antibodies to treat plasma cell malignancies, most notably multiple myeloma. This approach involves the simultaneous binding of B-cell maturation antigen (BCMA), which is highly expressed on the surface of malignant plasma cells, and the CD3 epsilon (CD3ε) subunit of the T-cell receptor complex on T-lymphocytes [1, 2]. By physically bridging these two cell types, the bispecific antibody creates an artificial immunological synapse that triggers T-cell activation and the subsequent release of cytotoxic granules, such as perforin and granzymes, into the target cell [1, 3]. This process results in the direct lysis of BCMA-positive tumor cells independent of major histocompatibility complex (MHC) recognition [5]. Clinically, this target has been successfully exploited by drugs like teclistamab and elranatamab, providing a potent treatment option for patients with relapsed or refractory disease [3, 4]. The specificity of BCMA for the B-cell lineage makes it an ideal target for minimizing off-target toxicity to other tissues [1]. However, the intense immune activation can lead to significant side effects, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [4]. Monitoring of soluble BCMA levels and T-cell subsets is often used to evaluate treatment efficacy and patient response [3]. This bridging strategy represents a significant advancement in immunotherapy for hematologic cancers.

Other names

BCMA-CD3TNFRSF17-CD3EB-cell maturation antigen-CD3 epsilon complexBCMA-CD3 bispecific antibody targetCD3E-TNFRSF17

Bispecific antibody-mediated T-cell redirection and activation