Kallikrein-3 (PSA) and PSA-derived peptide-MHC complexes (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 [1]. Its physiological function involves the proteolysis of semenogelins to facilitate the liquefaction of the seminal coagulum [1, 5]. In the context of oncology, PSA is a well-established biomarker for prostate cancer, but it also serves as a therapeutic target when its derived peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules [2, 3]. These PSA-peptide-MHC complexes are targeted by immunotherapies such as T-cell receptor (TCR) engineered T-cells and therapeutic vaccines like PROSTVAC, which aim to induce a cytotoxic T-lymphocyte response against cancer cells [4]. While PSA is highly specific to prostate tissue, therapeutic strategies must account for the fact that it is also expressed in normal prostate cells, potentially leading to on-target off-tumor effects [4]. Furthermore, the efficacy of targeting these complexes is often restricted by specific HLA types, such as HLA-A*02:01, which limits the eligible patient population [3]. Despite these challenges, PSA remains a primary focus for developing prostate-specific immunotherapies due to its high expression levels in malignant tissue [2].

Other names

Prostate-specific antigenKLK3Gamma-seminoproteinP-30 antigenSemenogelasePSA-peptide-MHC complex

Induction of antigen-specific T-cell mediated cytotoxicity against cells presenting PSA-derived peptides on MHC class I molecules.