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

基于全肿瘤裂解物或具有已验证的 HLA 结合的新表位的癌症疫苗优于具有预测的 HLA 结合亲和力的疫苗

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作者:Hajer Fritah, Michele Graciotti, Cheryl Lai-Lai Chiang, Anne-Laure Huguenin-Bergenat, Rémy Petremand, Ritaparna Ahmed, Philippe Guillaume, Julien Schmidt, Brian J Stevenson, David Gfeller, Alexandre Harari, Lana E Kandalaft

Abstract

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.

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