Mutant tumor protein p53 neoantigen peptide–major histocompatibility complex class I complex (Mutant TP53-MHC I complex)

Mutant tumor protein p53 (TP53) neoantigen peptide–major histocompatibility complex (MHC) class I complexes are highly specific targets for cancer immunotherapy, formed when mutated p53 fragments are presented on the cell surface (Hsiue et al., Science, 2021). TP53 is the most frequently mutated gene in human cancers, and specific hotspot mutations (e.g., R175H, R273H) create unique neoantigens that are absent in healthy tissues (Lo et al., JCI, 2020). These mutant peptides are processed and displayed by MHC class I molecules, such as HLA-A*02:01, allowing the immune system to selectively identify and eliminate malignant cells. Therapeutic strategies targeting these complexes include T-cell receptor (TCR)-engineered T cells, bispecific T-cell engagers (BiTEs), and neoantigen vaccines (Malekzadeh et al., JCI, 2019). For example, the bispecific antibody JNJ-78278343 is designed to target the p53 R175H/HLA-A*02:01 complex to trigger T-cell mediated lysis (ClinicalTrials.gov NCT04588324). However, the clinical application of these targets is limited by the requirement for specific HLA matching and the risk of immune escape through MHC downregulation or loss of heterozygosity.

Other names

p53 neoantigen-HLA complexMutant p53-HLA-A2 complexp53 R175H-HLA-A*02:01 complexp53 R273H-HLA-A*02:01 complexp53-MHC I neoepitope

Redirection of T-cell cytotoxicity toward cancer cells through specific recognition of mutant p53 peptides presented by MHC class I molecules.