Background: With the rise of immunotherapy based on cancer neoantigen, identification of neoepitopes has become an urgent problem to be solved. The TP53 R273C mutation is one of the hotspot mutations of TP53, however, the immunogenicity of this mutation is not yet clear. The aim of this study is to identify potential epitopes for p53R273C mutant.
Methods: In this study, bioinformatic methods, peptide exchange assay, and peptide-immunized human leukocyte antigen (HLA) transgenic mouse model were used to explore the immunogenicity of this mutation.
Results: Peptides with higher affinity to common HLA-A alleles (A*11:01, A*02:01) were discovered by computational prediction. All the 8-11 mer peptides contain the mutation site were synthesized and soluble peptides were used in the peptide exchange assay. However, the exchange efficiencies of these predicted peptides to HLAs were lower. Fortunately, other peptides with higher exchange efficiency were discovered. Then, the immunogenicity of these peptides was validated with the HLA-A2 transgenic mice model.
Conclusion: We identified three potential neoepitopes of p53R273C for HLA-A*02:01, one potential neoepitope for HLA-A*11:01 and no neoepitope for HLA-A*24:02.
Keywords: TP53 R273C mutation; immunogenicity; immunotherapy; neoantigen.
© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.