B-lymphocyte antigen CD20 and T-cell surface glycoprotein CD3 epsilon chain (CD20–CD3)

CD20–CD3 is a bispecific therapeutic target consisting of the B-lymphocyte antigen CD20 and the T-cell surface glycoprotein CD3 epsilon chain [1, 15]. CD20 is a four-pass transmembrane protein expressed on the surface of B-cells from the pre-B stage through mature B-cells, playing a role in B-cell activation and calcium signaling [1, 10]. CD3 is a multi-subunit protein complex associated with the T-cell receptor (TCR) that is essential for signal transduction and T-cell activation [1, 16]. Bispecific antibodies targeting CD20 and CD3 function by simultaneously binding to both antigens, thereby recruiting and activating cytotoxic T-cells to eliminate CD20-positive malignant B-cells [3, 5]. This mechanism of action, known as T-cell redirection, bypasses the requirement for MHC-mediated antigen presentation, making it highly effective in treating B-cell non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemia (CLL) [2, 7]. Therapeutic agents hitting this target, such as mosunetuzumab and glofitamab, have shown significant efficacy in relapsed or refractory settings, though they are associated with risks like cytokine release syndrome (CRS) and neurotoxicity [9, 14].

Other names

CD20/CD3MS4A1/CD3ECD20 x CD3CD20-CD3 bispecificCD20-CD3 T-cell engager

Bispecific T-cell engagement (BiTE) or bispecific antibody-mediated T-cell redirection. The drug simultaneously binds CD20 on B-cells and CD3 on T-cells, forming a cytolytic synapse that induces T-cell activation and subsequent lysis of the target B-cell, independent of MHC-TCR interaction [3, 5, 9].