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

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

doi:10.1016/j.isci.2023.106288

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.

Authors

Hajer Fritah^{1

2}, Michele Graciotti^{1

3

2}, Cheryl Lai-Lai Chiang^{1

2}, Anne-Laure Huguenin-Bergenat^{1

2}, Rémy Petremand^{1

2}, Ritaparna Ahmed^{1

2}, Philippe Guillaume^{1

3}, Julien Schmidt^{1

3}, Brian J Stevenson^{1

2

4}, David Gfeller^{1

2

4}, Alexandre Harari^{1

2}, Lana E Kandalaft^{1

3

2}

Affiliations

¹ Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland.
² Agora Cancer Research Center, Lausanne, Switzerland.
³ Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁴ SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.

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.

Keywords: Cancer; Immunity; Molecular medicine.