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

The BCMA–CD3 interface is a synthetic immunological synapse created by bispecific antibodies to treat plasma cell malignancies. BCMA (B-cell maturation antigen, also known as TNFRSF17) is a cell surface receptor highly expressed on malignant and healthy plasma cells, where it plays a critical role in cell survival and proliferation (UniProt Q02223) [1]. CD3 is a multi-subunit protein complex, specifically the epsilon subunit (CD3e), that serves as a T-cell co-receptor essential for signal transduction and T-cell activation (UniProt P07766) [2]. Drugs targeting this interface, such as Teclistamab and Elranatamab, utilize a bispecific format to physically bridge BCMA-expressing tumor cells with CD3-expressing cytotoxic T cells [3, 4]. This interaction triggers T-cell activation and the release of perforins and granzymes, leading to the targeted lysis of multiple myeloma cells regardless of major histocompatibility complex (MHC) expression [5]. While this therapeutic strategy has shown significant efficacy in relapsed or refractory multiple myeloma, it is frequently associated with systemic inflammatory toxicities like cytokine release syndrome (CRS) and increased infection risk due to the depletion of normal plasma cells [6]. Sources: [1] UniProt Consortium. TNFRSF17 - Tumor necrosis factor receptor superfamily member 17. https://www.uniprot.org/uniprotkb/Q02223/entry [2] UniProt Consortium. CD3E - T-cell surface glycoprotein CD3 epsilon chain. https://www.uniprot.org/uniprotkb/P07766/entry [3] FDA. Tecvayli (teclistamab-cqyv) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf [4] FDA. Elrexfio (elranatamab-bcmm) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf [5] Labrijn, A. F., et al. (2019). Bispecific antibodies: a mechanistic review of the pipeline. Nature Reviews Drug Discovery, 18(8), 585-608. [6] Moreau, P., et al. (2022). Teclistamab in Relapsed or Refractory Multiple Myeloma. New England Journal of Medicine, 387(6), 495-505.

Other names

TNFRSF17–CD3 interfaceBCMA–CD3eB-cell maturation antigen–T-cell receptor complexBCMA-CD3 bispecific target

Bispecific T-cell redirection and activation leading to MHC-independent tumor cell lysis