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

The T-cell surface glycoprotein CD3 epsilon chain–B-lymphocyte antigen CD20 protein–protein interface is a pharmacological target created by bispecific antibodies (BsAbs) to facilitate T-cell-mediated destruction of B cells. This interface is formed when a therapeutic agent simultaneously binds to the CD3 epsilon subunit of the T-cell receptor (TCR) complex on T lymphocytes and the CD20 (MS4A1) antigen on the surface of B lymphocytes [1, 2]. By physically bridging these two cells, the drug induces the formation of a synthetic cytolytic synapse, which bypasses the requirement for Major Histocompatibility Complex (MHC) class I recognition and redirects the cytotoxic activity of T cells toward CD20-positive cells [3, 4]. The resulting T-cell activation leads to the release of cytolytic proteins, such as granzymes and perforins, which induce apoptosis in the target B cell [5, 6]. This approach is primarily utilized in the treatment of B-cell malignancies, including diffuse large B-cell lymphoma and follicular lymphoma, particularly in relapsed or refractory settings [7]. While highly effective, the potent immune activation can lead to significant adverse effects, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [8]. Citations: [1] Sun, L. L., et al. (2020) Sci Transl Med; [2] Klein, C., et al. (2021) Expert Opin Biol Ther; [3] Budde, L. E., et al. (2022) Lancet Oncol; [4] Dickinson, M. J., et al. (2022) N Engl J Med; [5] Thieblemont, C., et al. (2023) J Clin Oncol; [6] Engelberts, P. J., et al. (2020) EBioMedicine; [7] Bannerji, R., et al. (2021) Lancet Oncol; [8] Lee, D. W., et al. (2019) Biol Blood Marrow Transplant.

Other names

CD20 x CD3CD3 x CD20T-cell engager targetCD3-CD20 bispecific targetCD3-CD20 complex

T-cell redirection and activation via bispecific antibody-mediated bridging of T cells and B cells