T-cell receptor recognizing Prostate-specific membrane antigen-derived peptide–MHC complexes (PSMA-specific TCR)

The T-cell receptor (TCR) recognizing PSMA-derived peptide–MHC complexes is a specialized immune receptor engineered to target Prostate-Specific Membrane Antigen (PSMA), a protein highly expressed in prostate cancer (Santoro et al., 2020). Unlike Chimeric Antigen Receptors (CARs) that recognize surface proteins directly, these TCRs identify intracellularly processed PSMA fragments presented as peptides by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01 (Schendel et al., 2020). This allows the immune system to target a broader range of antigens, including those derived from internal cellular proteins. Upon binding to the PSMA peptide-MHC complex, the TCR triggers T-cell activation, leading to the secretion of cytotoxic molecules like perforin and granzymes that induce apoptosis in the tumor cell (PubMed: 32661115). This target is primarily utilized in adoptive cell therapies, such as TCR-engineered T-cell (TCR-T) therapy, for patients with metastatic castration-resistant prostate cancer (ClinicalTrials.gov, NCT04464226). While highly specific, therapeutic challenges include potential on-target, off-tumor effects due to low-level PSMA expression in healthy tissues like the salivary glands and kidneys. Ongoing research aims to refine TCR affinity to maximize anti-tumor efficacy while minimizing systemic toxicity.

Other names

PSMA-specific T-cell receptorTCR-PSMAFOLH1-specific T-cell receptorPSMA-peptide-MHC-specific TCRGlutamate carboxypeptidase II-specific TCR

The TCR specifically binds to PSMA-derived peptides (e.g., PSMA:711-719) presented by MHC Class I molecules (typically HLA-A*02:01) on the surface of tumor cells, triggering T-cell activation and subsequent cytotoxic destruction of the target cell.