Prostate-specific membrane antigen-derived peptide-MHC complex (PSMA-pMHC)

Prostate-specific membrane antigen (PSMA)-derived peptide antigens presented on Major Histocompatibility Complex (MHC) molecules are specialized targets for cellular immunotherapy, particularly in prostate cancer (PubMed: 10491055). PSMA, a transmembrane glycoprotein also known as folate hydrolase 1 (FOLH1), is highly overexpressed in prostate adenocarcinoma and the neovasculature of various solid tumors (UniProt: Q04609). These targets are formed when PSMA protein is intracellularly processed into short peptide fragments and loaded onto MHC Class I molecules, such as HLA-A*02:01, for presentation on the cell surface (PubMed: 11062450). This presentation enables the recognition of cancer cells by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes. Unlike monoclonal antibodies or CAR-T cells that bind to the surface-exposed protein structure, therapies targeting the PSMA-pMHC complex—such as TCR-engineered T cells and peptide vaccines—can target epitopes derived from any part of the protein, offering a distinct mechanism for immune engagement (PubMed: 16103051). Safety considerations include potential on-target off-tumor toxicity in tissues with low-level PSMA expression, such as the salivary glands and kidneys, as well as the risk of cross-reactivity with similar self-peptides.

Other names

PSMA-derived HLA-restricted peptidesPSMA-MHC complexPSMA epitopesFOLH1-derived peptide-MHC

T-cell receptor (TCR) mediated recognition of HLA-restricted PSMA peptides leading to T-cell activation and tumor cell lysis.