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
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.
