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

The T-cell receptor (TCR) recognizing PSA-derived peptides presented by MHC molecules is a key component of engineered T-cell therapies designed to treat prostate cancer. Prostate-specific antigen (PSA), or KLK3, is a well-known biomarker and tissue-specific protein that is highly expressed in prostate adenocarcinoma. Peptides derived from PSA, such as the HLA-A*02:01-restricted epitope KLQCVDLHV, are processed and presented on the surface of tumor cells, where they can be recognized by high-affinity TCRs. In TCR-T cell therapy, these specific TCR sequences are cloned and expressed in a patient's peripheral blood T cells to redirect their cytotoxic activity against the tumor. Once these engineered T cells encounter the PSA-peptide-MHC complex, they undergo activation and release effector molecules like interferon-gamma and granzyme B to induce tumor cell lysis. This approach aims to overcome the immune cold nature of the prostate tumor microenvironment by providing a robust, antigen-specific T-cell population. However, clinical development faces challenges such as potential on-target, off-tumor toxicity due to PSA expression in normal prostate tissue and the risk of TCR cross-reactivity with similar self-peptides.

Other names

KLK3-specific T-cell receptorPSA-TCRT-cell receptor recognizing KLK3-derived peptidesPSA-specific TCR-T

Engineered T cells expressing the TCR recognize PSA-derived peptides presented by MHC class I molecules on tumor cells, leading to T-cell activation and targeted cell lysis.