MHC class I HLA-A*02:01-restricted T-cell receptor specific for PSMA and TARP epitopes (PSMA/TARP-specific TCR)

MHC class I HLA-A2–restricted T-cell receptors (TCRs) specific for PSMA and TARP epitopes are specialized immune receptors utilized in adoptive cellular immunotherapy for the treatment of prostate and breast cancers [Journal of Immunotherapy, 2016]. These TCRs are engineered to recognize specific peptide fragments derived from Prostate-Specific Membrane Antigen (PSMA) and TCR Gamma Alternate Reading Frame Protein (TARP) when presented by the Human Leukocyte Antigen A2 (HLA-A2) molecule [Cancer Research, 2017]. PSMA is a transmembrane protein significantly upregulated in nearly all stages of prostate cancer, while TARP is a protein product of an alternate reading frame of the TCR gamma locus, predominantly expressed in prostate and breast malignancies [National Cancer Institute]. Upon binding to their cognate peptide-MHC complexes on the surface of tumor cells, these TCRs trigger T-cell activation, leading to the release of cytotoxic granules and pro-inflammatory cytokines [PubMed]. This targeted approach aims to provide a precise and potent immune response against solid tumors that are often resistant to conventional therapies [ClinicalTrials.gov]. Clinical development focuses on TCR-T cell therapies where a patient's own T cells are modified to express these receptors to achieve durable anti-tumor activity [Nature Reviews Drug Discovery].

Other names

PSMA-specific T-cell receptorTARP-specific T-cell receptorHLA-A2 restricted TCRProstate-specific membrane antigen T-cell receptorTCR gamma alternate reading frame protein T-cell receptorPSMA/TARP TCR-T

Engineered T cells expressing these TCRs recognize and bind to specific peptide-MHC complexes (PSMA or TARP peptides presented by HLA-A*02:01) on the surface of tumor cells, which triggers intracellular signaling through the CD3 complex, leading to T-cell activation, the release of cytotoxic granules (perforin/granzymes), and targeted cell lysis [PubMed, 2017].