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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Epitope identification for p53R273C mutant.

Jian Zhang1,2,3, Minglu Liu2, Yin Chen3

  • 1School of Medicine, Nankai University, Tianjin, China.

Immunity, Inflammation and Disease
|January 27, 2023
PubMed
Summary
This summary is machine-generated.

This study identifies potential neoepitopes from the TP53 R273C mutation, crucial for developing cancer neoantigen immunotherapies. Researchers found specific neoepitopes for HLA-A*02:01 and HLA-A*11:01 alleles.

Keywords:
TP53 R273C mutationimmunogenicityimmunotherapyneoantigen

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Area of Science:

  • Oncology
  • Immunology
  • Bioinformatics

Background:

  • Neoantigen identification is critical for cancer immunotherapy development.
  • The immunogenicity of the TP53 R273C mutation, a common TP53 hotspot, remains unclear.
  • This study aims to identify potential neoepitopes arising from the p53R273C mutation.

Purpose of the Study:

  • To identify potential neoepitopes derived from the TP53 R273C mutation.
  • To assess the immunogenicity of these potential neoepitopes.
  • To aid in the development of personalized cancer immunotherapies.

Main Methods:

  • Bioinformatic prediction of peptides with high affinity to common HLA-A alleles (A*11:01, A*02:01).
  • Peptide synthesis and validation using peptide exchange assays.
  • Immunogenicity assessment in a human leukocyte antigen (HLA)-A2 transgenic mouse model.

Main Results:

  • Computational prediction identified peptides with high affinity to HLA-A*11:01 and HLA-A*02:01.
  • Peptide exchange assays revealed peptides with higher exchange efficiency.
  • Validation in HLA-A2 transgenic mice confirmed immunogenicity of selected peptides.
  • Identified three potential neoepitopes for HLA-A*02:01 and one for HLA-A*11:01.

Conclusions:

  • Three potential neoepitopes for p53R273C were identified for HLA-A*02:01.
  • One potential neoepitope for p53R273C was identified for HLA-A*11:01.
  • No neoepitopes were identified for HLA-A*24:02, suggesting allele-specific presentation.