Cancer vaccines based on whole-tumor lysate or neoepitopes with validated HLA binding outperform those with predicted HLA-binding affinity

Antigen selection and prioritization represent crucial determinants of vaccines' efficacy. Here, we compare two personalized dendritic cell-based vaccination strategies using whole-tumor lysate or neoantigens. Data in mouse and in cancer patients demonstrate that peptide vaccines using neoantigens predicted on the sole basis of in silico peptide-major histocompatibility complex (MHC) binding affinity underperform relative to whole-tumor-lysate vaccines. In contrast, effec-tive in vitro peptide-MHC binding affinity and peptide immunogenicity signifi-cantly improve the prioritization of tumor-rejecting neoepitopes and result in more efficacious vaccines.

Automated summary

Antigen selection is important for vaccines' efficacy. A comparison of two dendritic cell-based vaccination strategies showed that peptide vaccines using neoantigens predicted on the basis of in silico peptide-MHC binding affinity do not perform well compared to whole-tumor-lysate vaccines. However, prioritizing tumor-rejecting neoepitopes based on effective in vitro peptide-MHC binding affinity and peptide immunogenicity leads to more effective vaccines.