Prostate-specific membrane antigen and CD3 epsilon subunit (PSMA x CD3ε)

Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a type II transmembrane glycoprotein that is significantly overexpressed on the surface of prostate cancer cells, particularly in advanced and metastatic stages (UniProt Q04609). CD3 epsilon (CD3ε) is a vital subunit of the T-cell receptor (TCR) complex required for T-cell activation and signal transduction (UniProt P07766). The simultaneous targeting of PSMA on tumor cells and CD3ε on T cells is a therapeutic strategy employed by bispecific T-cell engagers (BiTEs) to treat metastatic castration-resistant prostate cancer (mCRPC). By binding to both PSMA and CD3ε, these agents facilitate the formation of an immunological synapse, leading to T-cell activation and the subsequent release of perforins and granzymes to induce tumor cell lysis (PubMed: 33023538). This mechanism allows for potent, targeted immune-mediated destruction of cancer cells regardless of MHC expression. Clinical development of drugs targeting this pair focuses on overcoming the immunosuppressive tumor microenvironment while managing side effects like cytokine release syndrome and off-target binding in tissues like the salivary glands and kidneys (PubMed: 34155011).

Other names

FOLH1Glutamate carboxypeptidase 2GCPIICD3ET-cell surface glycoprotein CD3 epsilon chainNAALADase IProstate-specific membrane peptidaseT3E

Bispecific T-cell engagement (BiTE) resulting in redirected T-cell mediated cytotoxicity against PSMA-expressing tumor cells