Mutant p53 peptide-HLA complex (mut-p53/HLA complex)

The mutant p53 peptide-HLA complex is a tumor-specific neoantigen formed when mutated p53 proteins are degraded by the proteasome and their resulting peptides are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules. As TP53 is the most frequently mutated gene in human cancers, these complexes serve as critical targets for precision immunotherapy, particularly for 'hotspot' mutations like R175H and R248Q that are shared across many patients. Unlike wild-type p53, which is expressed at low levels in normal cells, mutant p53 often accumulates in high concentrations in tumor cells, leading to the presentation of these unique neoepitopes. Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (TCEs) designed to recognize the specific peptide-HLA conformation with high affinity. These treatments aim to redirect the immune system to selectively eliminate cancer cells while sparing healthy tissues that lack the specific mutation or present only wild-type p53 peptides.

Other names

p53 neoantigenMutant p53-MHC complexp53-derived neoepitopep53 R175H/HLA-A*02:01 complexp53 R248Q/HLA-A*11:01 complexp53 R248W/HLA-A*02:01 complexMutation-associated neoantigen (MANA)

T-cell redirection via bispecific T-cell engager; Adoptive T-cell therapy with TCR-engineered T cells; Immune system priming via neoantigen vaccines