Cellular tumor antigen p53-derived peptide-MHC complex (p53-pMHC)

The cellular tumor antigen p53-derived peptide-MHC complex is a molecular target formed when fragments of the p53 protein are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I or II molecules. As p53 is the most frequently mutated gene in human cancer, these complexes often display neoantigens (mutant peptides) or overexpressed wild-type peptides that are absent or rare on normal tissues (PMID: 27345415, PMID: 33649130). On tumor cells, these complexes serve as specific markers for recognition by cytotoxic T-lymphocytes, while on dendritic cells, they are essential for priming the adaptive immune response (PMID: 17510436). Therapeutic strategies targeting this complex include p53-based vaccines, TCR-engineered T-cells, and TCR-like bispecific antibodies designed to trigger a potent and specific anti-tumor immune attack (PMID: 30012515). This target is particularly valuable because it allows for the therapeutic targeting of an intracellular protein, which is otherwise difficult to reach with traditional antibodies, by exploiting the natural antigen presentation pathway. Successful targeting depends heavily on the patient's HLA genotype and the specific mutation profile of the TP53 gene.

Other names

p53-HLA complexp53-derived epitopesp53 neoantigen-MHC complexp53-MHC class I/II complexTumor protein p53-derived peptides presented by MHC

Recognition of p53-derived peptides presented by MHC molecules by T-cell receptors (TCRs) or TCR-like molecules, leading to the activation of cytotoxic T-lymphocytes and subsequent lysis of tumor cells (PMID: 33649130).