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

iScience (Apr 2023)

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

Affiliations

Hajer Fritah: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Michele Graciotti: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Cheryl Lai-Lai Chiang: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Anne-Laure Huguenin- Bergenat: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Rémy Petremand: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Ritaparna Ahmed: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland
Philippe Guillaume: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Julien Schmidt: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
Brian J. Stevenson: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
David Gfeller: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland; SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Alexandre Harari: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland; Corresponding author
Lana E. Kandalaft: Ludwig Institute for Cancer Research, Lausanne Branch, and Department of Oncology, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, 1011, Switzerland; Center of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland; Agora Cancer Research Center, Lausanne, Switzerland; Corresponding author

Journal volume & issue: Vol. 26, no. 4
p. 106288

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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