Prostate-specific membrane antigen (PSMA) and CD3 T-cell receptor complex (PSMA x CD3 complex)

The Prostate-specific membrane antigen (PSMA) and CD3 T-cell receptor complex is a therapeutic target assembly formed by the simultaneous engagement of tumor-associated PSMA and the T-cell CD3 complex by multispecific antibodies [1, 2]. PSMA, also known as Folate Hydrolase 1 (FOLH1), is a transmembrane glycoprotein that is highly overexpressed in prostate cancer cells and the neovasculature of solid tumors, while having limited expression in normal tissues such as the salivary glands and kidneys [1, 3]. CD3 is a multi-subunit protein complex, specifically the epsilon chain (CD3E), which is essential for T-cell receptor signaling and activation [2]. When a bispecific T-cell engager (BiTE) or similar molecule binds both PSMA and CD3, it facilitates the formation of a cytolytic immune synapse between a cytotoxic T cell and a tumor cell [3, 5]. This interaction bypasses the need for traditional MHC-I antigen presentation, leading to direct T-cell activation, the release of perforins and granzymes, and subsequent tumor cell lysis [4, 5]. This target complex is a primary focus for treating metastatic castration-resistant prostate cancer (mCRPC), with several agents currently in clinical development [3, 4].

Other names

PSMA/CD3 complexPSMA-CD3 bispecific targetFOLH1/CD3E complexPSMA-CD3 T-cell engager complexPSMA-CD3 cytolytic synapse

Bispecific T-cell redirection leading to MHC-independent T-cell activation and tumor cell cytolysis