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

iScience. 2023 Feb 27;26(4):106288. doi: 10.1016/j.isci.2023.106288. eCollection 2023 Apr 21.


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, effective in vitro peptide-MHC binding affinity and peptide immunogenicity significantly improve the prioritization of tumor-rejecting neoepitopes and result in more efficacious vaccines.

Keywords: Cancer; Immunity; Molecular medicine.