Tumor protein p53-derived epitope (p53 epitope)

Tumor protein p53 (TP53)-derived epitopes are peptide fragments of the p53 protein presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (PubMed: 33616149). In the context of oncology, these epitopes often arise from hotspot mutations in the TP53 gene, creating neoantigens that are unique to tumor cells and can be recognized by T-cell receptors (TCRs) (PubMed: 30635454). These neoepitopes are highly attractive targets for immunotherapy because TP53 is the most frequently mutated gene in human cancers, including ovarian, colorectal, and lung carcinomas (NIH: National Cancer Institute). Therapeutic approaches targeting these epitopes include TCR-engineered T-cell therapies, which are designed to recognize specific p53 mutation-HLA complexes, and cancer vaccines like p53-MVA intended to prime the patient's own immune system (ClinicalTrials.gov: NCT02432963). Because wild-type p53 is expressed at low levels in normal tissues, targeting mutation-specific epitopes minimizes the risk of off-target toxicity. However, the diversity of HLA alleles and the variety of TP53 mutations necessitate a personalized or off-the-shelf library approach to treatment.

Other names

p53 neoantigenp53-derived peptidep53 T-cell epitopeTP53-derived antigenp53-derived HLA-restricted peptide

Induction of antigen-specific T-cell mediated cytotoxicity against tumor cells presenting p53-derived peptides on MHC molecules (PubMed: 30635454).