Mutant tumor protein p53-derived neoantigen peptides presented by human leukocyte antigen (HLA) class I alleles (Mutant TP53-HLA complex)

Mutant tumor protein p53 (TP53)-derived neoantigen peptides presented by specific human leukocyte antigen (HLA) class I alleles are critical targets in modern oncology. TP53 is the most frequently mutated gene in human cancers, often involving "hotspot" missense mutations that lead to the accumulation of stable, mutant p53 protein in tumor cells (Lo et al., 2019, Science). These mutant proteins are processed into short peptides and presented on the cell surface by HLA class I molecules, where they can be recognized as "non-self" by the immune system (Malekzadeh et al., 2019, Clinical Cancer Research). Because these neoantigens are exclusively expressed by malignant cells and are absent in healthy tissues, they provide a high degree of therapeutic selectivity. Current drug development strategies include T-cell receptor (TCR) engineered T-cell therapies, bispecific antibodies, and personalized cancer vaccines designed to elicit a cytotoxic T-lymphocyte response against these specific peptide-MHC complexes (Hsiue et al., 2021, Science). These therapies aim to bypass the immune tolerance often associated with wild-type p53 by targeting the unique sequence changes in the mutant protein. However, the efficacy of these treatments is highly dependent on the patient's specific HLA haplotype and the presence of the corresponding TP53 mutation, necessitating precise patient stratification.

Other names

TP53 neoantigensp53 mutant neoepitopesHLA-restricted p53 mutantsMutant p53-MHC complexesp53 hotspot mutation neoantigens

Recognition of the peptide-MHC complex by engineered or endogenous T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte (CTL) mediated lysis of tumor cells.