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Identification of public neoantigens with broad HLA class I coverage as candidates for off-the-shelf cancer vaccine development in colorectal cancer - PubMed

5 days ago
  • #immunotherapy
  • #colorectal cancer
  • #neoantigens
  • Identification of public neoantigens with broad HLA class I coverage for off-the-shelf cancer vaccine development in colorectal cancer.
  • Development of a colorectal cancer-specific neoantigen panel integrating TCGA mutation data with HLA class I binding predictions across 68 alleles.
  • Evaluation of candidate neoantigens in a Vietnamese CRC cohort (n=67) based on mutation and HLA matching.
  • Functional immunogenicity assessed in patient-derived CD8+ T cells using IFN-γ ELISpot assays and single-cell RNA sequencing.
  • Panel comprised 73 recurrent nonsynonymous mutations, achieving >90% population coverage in Asian and Caucasian groups.
  • 58% of patients in the Vietnamese CRC cohort harbored at least one matched neoantigen.
  • Functional validation demonstrated robust CD8+ T-cell responses against TP53_R273H.
  • Neoantigen-reactive T cells exhibited cytotoxic effector function and stem-like memory phenotypes.
  • TP53_R273H identified as a clinically relevant shared neoantigen in CRC.
  • Integrative computational and experimental framework supports translational feasibility of population-tailored neoantigen panels.