T-cell receptor complex recognizing Prostate-Specific Antigen (PSA) peptide presented on MHC molecules (PSA-specific TCR)

The T-cell receptor (TCR) complex recognizing Prostate-Specific Antigen (PSA) peptides presented on MHC molecules is a specialized immune component utilized in adoptive cell therapies for prostate cancer. PSA is a glycoprotein almost exclusively produced by the epithelial cells of the prostate gland and is highly overexpressed in prostate adenocarcinoma, making it an ideal target for redirected T-cell attacks. The TCR complex consists of alpha and beta chains that specifically bind to PSA-derived peptides, such as the immunodominant PSA:154-163 sequence, when they are displayed by Human Leukocyte Antigen (HLA) molecules on the cell surface. This recognition event is the critical first step in the activation of engineered T-cells, which then execute a cytotoxic program to eliminate the malignant cells. In a clinical context, this target is primarily addressed through TCR-engineered T-cell (TCR-T) therapies, where a patient's own immune cells are modified to express the high-affinity PSA-specific receptor. While promising for treating metastatic castration-resistant prostate cancer, therapeutic development must carefully manage risks such as cytokine release syndrome and potential cross-reactivity with similar endogenous peptides.

Other names

PSA-specific T-cell receptorTCR recognizing PSA/HLA complexProstate-specific antigen-targeted T-cell receptorPSA-TCR

The mechanism involves the engineering of patient T-cells to express a specific T-cell receptor (TCR) that recognizes PSA peptides (such as PSA:154-163) presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01. Upon binding to the PSA-MHC complex on the surface of prostate cancer cells, the TCR triggers T-cell activation, leading to the release of cytotoxic granules (perforin and granzymes) and cytokines, which results in the targeted lysis of the tumor cells.