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

The Prostate-specific antigen-specific T-cell receptor (PSA-TCR) is a recombinant or naturally derived antigen receptor engineered into T lymphocytes to direct their cytotoxic activity against prostate cancer cells. PSA, also known as Kallikrein-3 (KLK3), is a well-characterized biomarker and tumor-associated antigen that is highly expressed in both localized and metastatic prostate cancer (PMID: 28453471). The PSA-TCR specifically recognizes processed PSA peptides, such as the immunodominant PSA 141-149 sequence, when presented by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 (PMID: 11507058). Upon binding to the peptide-MHC complex, the TCR initiates a signaling cascade through the CD3 complex, leading to the activation of the T cell and the subsequent release of cytotoxic molecules like granzymes and perforin to eliminate the target cell. This therapeutic approach, known as TCR-T cell therapy, is primarily investigated for patients with metastatic castration-resistant prostate cancer (mCRPC) who have failed standard therapies (NCT03150719). Clinical development focuses on optimizing TCR affinity and ensuring specificity to minimize off-target effects on healthy tissues. Challenges in this field include maintaining T-cell persistence in the immunosuppressive tumor microenvironment and managing potential toxicities such as cytokine release syndrome (PMID: 30635454).

Other names

KLK3-specific T-cell receptorPSA-specific TCRPSA-targeted T-cell receptorProstate-specific antigen-directed T-cell receptor

Engineered T-cells express a specific TCR that recognizes PSA-derived peptides presented by HLA-A*02:01, triggering T-cell activation and direct lysis of PSA-expressing tumor cells.