HLA-A*02:01-restricted Prostate-specific membrane antigen epitope (HLA-A2/PSMA epitope)

The HLA-A*02:01-restricted Prostate-specific membrane antigen (PSMA) epitope is a molecular complex consisting of a specific peptide fragment derived from the PSMA protein bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule. PSMA, also known as folate hydrolase 1 (FOLH1), is a transmembrane glycoprotein that is highly overexpressed in prostate cancer cells and the neovasculature of various solid tumors (PMID: 10511130). In HLA-A*02:01-positive individuals, intracellular processing of PSMA generates short peptides, such as PSMA 27-35 (VLLHETDSV) or PSMA 663-671 (MMKAFLDEL), which are transported to the cell surface for presentation to the immune system (PMID: 11156514). This peptide-MHC complex serves as a critical target for T-cell-based immunotherapies, including T-cell receptor (TCR) engineered T-cells and peptide vaccines, which aim to trigger a cytotoxic T-lymphocyte (CTL) response against malignant cells (PMID: 10667477). Unlike monoclonal antibodies that target the extracellular domain of PSMA, therapies directed at this epitope can recognize antigens derived from the entire PSMA protein sequence. This target is particularly relevant for treating metastatic castration-resistant prostate cancer (mCRPC) in patients carrying the HLA-A*02:01 allele. Ongoing research focuses on improving the affinity of TCRs for this complex and overcoming the immunosuppressive tumor microenvironment to enhance therapeutic efficacy (PMID: 12183333).

Other names

PSMA:HLA-A*02:01 complexPSMA-derived HLA-A2 restricted peptideProstate-specific membrane antigen epitopeFOLH1 epitopePSMA 27-35 epitopePSMA 663-671 epitope

Induction of cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells through specific recognition of the peptide-MHC complex by T-cell receptors (TCRs) or TCR-like molecules.