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

The CD20–CD3 interface is a therapeutic target created by bispecific antibodies (BsAbs) designed to bridge B-lymphocytes and T-lymphocytes. This interface involves the simultaneous binding of the B-lymphocyte antigen CD20, a four-transmembrane protein involved in B-cell development, and the CD3 epsilon subunit of the T-cell receptor (TCR) complex [4, 5]. By physically linking these two cells, the bispecific molecule induces the formation of an artificial immunological synapse, which triggers T-cell activation and the subsequent release of cytotoxic granules like perforin and granzymes into the B-cell [4]. This process, known as T-cell redirected cytotoxicity (TRCC), occurs independently of Major Histocompatibility Complex (MHC) class I presentation, allowing the immune system to bypass common tumor escape mechanisms [4]. Drugs targeting this interface, such as Mosunetuzumab and Glofitamab, are primarily utilized in the treatment of relapsed or refractory B-cell malignancies, including various forms of Non-Hodgkin Lymphoma [1, 2]. While highly effective, the potent activation of T-cells can result in significant adverse events, most notably cytokine release syndrome (CRS) and neurotoxicity (ICANS), requiring careful clinical management [1, 3].

Other names

CD20 x CD3CD3 x CD20CD20/CD3 bispecific targetCD20-CD3 T-cell engagerB-cell/T-cell synapse

T-cell redirected cytotoxicity (TRCC) via the formation of an artificial immunological synapse between CD20-positive B-cells and CD3-positive T-cells, leading to MHC-independent T-cell activation and target cell lysis [4].