Prostate-specific antigen (PSA) peptide-MHC complex (PSA-pMHC)

Prostate-specific antigen (PSA), also known as Kallikrein-3 (KLK3), is a serine protease primarily produced by the epithelial cells of the prostate gland (UniProt: P07288). While PSA is a well-known secreted biomarker for prostate cancer, it also serves as a source of intracellularly processed peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, such as HLA-A*02:01 (PubMed: 10438424). These PSA peptide-MHC (pMHC) complexes are the specific targets for T-cell receptors (TCRs) on cytotoxic T lymphocytes. Therapeutic strategies, including TCR-engineered T-cell (TCR-T) therapies and vaccines like PROSTVAC-VF, are designed to recognize these complexes to induce a targeted immune response against PSA-expressing tumor cells (PubMed: 28811304, PubMed: 20406920). This approach allows for the targeting of an intracellular protein that is otherwise inaccessible to traditional antibody-based therapies. A primary safety concern is on-target, off-tumor toxicity to normal prostate tissue, although this is often mitigated in patients who have already undergone prostatectomy.

Other names

Kallikrein-3 (KLK3) peptide-HLA complexPSA-HLA-A*02:01 complexPSA-derived peptide-MHCPSA-pMHC

T-cell receptor (TCR) mediated recognition of specific PSA peptides presented on MHC Class I molecules, triggering cytotoxic T-lymphocyte (CTL) activation and targeted lysis of tumor cells.