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

Prostate-specific antigen (PSA), also known as Kallikrein-3 (KLK3), is a serine protease primarily expressed in the prostate and overexpressed in prostate cancer [UniProt: P07288]. PSA-derived peptides are processed and presented on the cell surface by MHC class I molecules, forming a peptide-MHC (pMHC) complex [PubMed: 9290717]. This pMHC complex is specifically recognized by T cell receptors (TCRs) on cytotoxic T lymphocytes, initiating an immune response against the cell [PubMed: 21602510]. As a therapeutic target, this complex is utilized in the development of cancer vaccines and adoptive cell therapies [PubMed: 20124481]. For example, the PROSTVAC vaccine uses viral vectors to stimulate T cells to recognize PSA-pMHC complexes on tumor cells [PubMed: 24501013]. TCR-engineered T cell (TCR-T) therapies are also being investigated to enhance the precision and potency of the immune attack against these targets [PubMed: 30108114]. The primary clinical application is the treatment of metastatic castration-resistant prostate cancer [PubMed: 20124481]. Potential safety concerns include autoimmune-mediated prostatitis and the risk of on-target off-tumor effects in tissues with low PSA expression [PubMed: 15150596]. Efficacy can be hindered by tumor-mediated HLA downregulation or an immunosuppressive microenvironment [PubMed: 21602510].

Other names

PSA peptide-HLA complexKallikrein-3 peptide-MHC complexPSA-derived epitope-MHC complexKLK3-pMHC

Induction of T cell-mediated cytotoxicity through the recognition of PSA-derived epitopes presented by MHC molecules on the surface of tumor cells.