Tumor protein p53 (264-272) peptide presented by HLA-A*02:01 (p53(264-272)/HLA-A*02:01)

The p53(264-272) peptide presented by HLA-A*02:01 is a tumor-associated antigen complex that serves as a critical target for cancer immunotherapy. The peptide sequence, LLGRNSFEV, is derived from the p53 protein, a master regulator of the cell cycle and the most frequently mutated gene in human cancers (PubMed: 15604258). While p53 is an intracellular protein and thus inaccessible to conventional monoclonal antibodies, its proteolytic fragments are presented on the cell surface by the HLA-A*02:01 major histocompatibility complex (MHC) class I molecule (PubMed: 8144904). This presentation allows for the recognition of malignant cells by the cellular immune system, specifically CD8+ T-cells. Therapeutic interventions such as TCR-engineered T-cells (TCR-T) and TCR-mimetic bispecific antibodies, like PM-p53, are designed to bind this specific peptide-MHC (pMHC) complex with high affinity (Phanes Therapeutics; ClinicalTrials.gov: NCT05534100). These drugs aim to trigger a potent immune response against tumors that overexpress or harbor specific mutations in p53, while sparing healthy tissues that do not present the antigen at sufficient levels. Current clinical applications target a variety of solid tumors, including ovarian, lung, and breast cancers, in patients who are HLA-A*02:01 positive (PubMed: 33723019).

Other names

LLGRNSFEV/HLA-A*02:01 complexp53-R264-272/HLA-A2p53 peptide-MHC complexp53(264-272) pMHC

T-cell receptor (TCR) or TCR-mimetic binding to the peptide-MHC complex to induce T-cell mediated cytotoxicity against tumor cells.