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

The CD20–CD3 cell–cell interface is a synthetic immunological synapse formed by bispecific antibodies to redirect T-cell cytotoxicity against B-cells (Labrijn et al., 2019). This interface involves the simultaneous binding of a therapeutic agent to B-lymphocyte antigen CD20 (MS4A1) on B-lymphocytes and the T-cell surface glycoprotein CD3 epsilon (CD3E) on T-cells (UniProt P11836, P07766). By bridging these two cell types, the interface bypasses the requirement for Major Histocompatibility Complex (MHC) class I recognition, allowing for the direct activation of T-cells regardless of TCR specificity (Dickinson et al., 2022). Upon formation of the interface, the T-cell undergoes activation, leading to the release of cytotoxic granules containing perforins and granzymes that induce apoptosis in the target B-cell (Budde et al., 2022). This therapeutic strategy is primarily employed in the treatment of B-cell malignancies, such as follicular lymphoma and diffuse large B-cell lymphoma (Hutchings et al., 2021). Clinically approved bispecific antibodies, including mosunetuzumab and glofitamab, are designed to stabilize this interface to achieve potent anti-tumor activity (FDA, 2022; FDA, 2023). However, the rapid and potent activation of T-cells at this interface can lead to systemic inflammatory responses, most notably cytokine release syndrome (CRS) and neurotoxicity (Lee et al., 2019).

Other names

CD20–CD3 cell–cell interfaceCD20xCD3 complexCD20-CD3 immunological synapseB-cell/T-cell bridgeCD20-CD3 T-cell engaging interface

Bispecific antibodies bind simultaneously to CD20 on B-cells and CD3 on T-cells, creating a synthetic synapse that triggers T-cell activation and subsequent B-cell lysis.