Mutant TP53 R175H peptide–HLA-A*02:01 complex (p53 R175H–HLA-A*02:01)

The mutant TP53 R175H peptide–HLA-A*02:01 complex is a tumor-specific neoantigen formed when the p53 protein, harboring the R175H mutation (most commonly with the peptide sequence HMTEVVRHC), is processed intracellularly and the resulting mutant peptide is presented on the cell surface by the MHC class I molecule HLA-A*02:01. This presentation creates a highly specific target for immune therapeutics, as the mutant peptide is not present in normal cells and is only displayed in tumors with the specific TP53 mutation and HLA-A*02:01 haplotype. Therapies such as bispecific antibodies (e.g., CLSP-1025) and TCR-mimic antibodies are in development to target this neoantigen–MHC complex, aiming to induce selective immune responses against cancer cells while sparing normal tissue.

Other names

p53 R175H neoantigen–HLA-A*02:01 complexTP53 R175H neoantigenHLA-A*02:01/p53 R175HHLA-A*02:01–p53 mutant complexanti-HLA-A*02:01/p53 R175H

T-cell redirection/activation via bispecific antibodies (engaging both the mutant peptide–MHC and CD3 on T cells); Immune-mediated lysis of cancer cells presenting this neoantigen; Potentially TCR-based therapies recognizing the complex