Prostate-specific antigen-specific T cell receptor (PSA-TCR)

The Prostate-specific antigen-specific T cell receptor (PSA-TCR) refers to a specialized immune receptor engineered to recognize peptides derived from the Prostate-Specific Antigen (PSA), a protein encoded by the KLK3 gene (UniProt P07288). PSA is a lineage-specific antigen highly expressed in prostate tissue and upregulated in prostate adenocarcinoma, making it a primary target for TCR-engineered T-cell (TCR-T) therapies (PubMed: 32541024). This specific TCR is notable for its ability to recognize PSA-derived peptides (such as PSA:161-175) presented by both MHC class I (e.g., HLA-A*02:01) and MHC class II (e.g., HLA-DRB1*01:01) molecules, potentially allowing for the simultaneous activation of cytotoxic and helper T-cell responses (PubMed: 11046056). The therapeutic mechanism involves the formation of an immunological synapse upon peptide-MHC recognition, leading to T-cell activation, the release of pro-inflammatory cytokines, and the targeted lysis of malignant cells (ClinicalTrials.gov: NCT03970382). Clinical development of PSA-TCR therapies faces challenges such as 'on-target, off-tumor' toxicity against healthy prostate tissue and the requirement for precise HLA matching in patients (PubMed: 28923894). Despite these challenges, the dual-MHC recognition capability offers a promising strategy for enhancing the durability and efficacy of immunotherapy in prostate cancer.

Other names

Prostate-specific antigen-specific T-cell receptorKLK3-specific T-cell receptorPSA-targeted T-cell receptorT cell receptor recognizing PSA-derived peptide

Engineered T cells expressing the PSA-TCR recognize PSA-derived peptides presented by MHC class I or II molecules on the surface of prostate cancer cells, leading to T cell activation, cytokine release, and targeted destruction of the tumor cells.