p53-derived peptide epitopes presented on MHC class I (p53-pMHC)

p53-derived peptide epitopes presented on MHC class I represent a critical class of tumor-associated antigens and neoantigens used in cancer immunotherapy. The p53 protein, often called the guardian of the genome, is the most frequently mutated gene in human cancers, leading to the presentation of unique mutant peptides (neoepitopes) or overexpressed wild-type peptides on the cell surface via Major Histocompatibility Complex (MHC) molecules. These peptide-MHC (pMHC) complexes serve as specific flags that can be recognized by the immune system, particularly by CD8+ cytotoxic T cells. Therapeutic strategies targeting these epitopes include TCR-engineered T-cell therapies (TCR-T), bispecific T-cell engagers (BiTEs), and therapeutic vaccines designed to elicit a robust anti-tumor immune response. Because many p53 mutations are hotspots shared across different patients and cancer types, these epitopes are highly attractive targets for off-the-shelf precision immunotherapies. However, challenges remain regarding the low density of these complexes on the cell surface and the potential for immune evasion through MHC downregulation.

Other names

p53 peptide-MHC complexp53-HLA complexp53 neoantigensp53 tumor-associated antigensp53-derived HLA-restricted antigens

Targeting of specific p53-derived peptides presented by MHC Class I molecules to induce T-cell mediated lysis of tumor cells.