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A comprehensive library of canonical and non-canonical MHC class I antigens for cancer vaccine development

View ORCID ProfileGeorges Bedran, Tongjie Wang, Dominika Pankanin, Kenneth Weke, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Catia Pesquita, Håkan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Palkowski, Maciej Pawlik, Maciej Parys, Robert O’Neill, Paul M. Brennan, Stefan Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fahraeus, Ted R. Hupp, Sachin Kote, View ORCID ProfileJavier A. Alfaro
doi: https://doi.org/10.1101/2022.01.13.475872
Georges Bedran
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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  • ORCID record for Georges Bedran
Tongjie Wang
2School of Informatics, University of Edinburgh, Edinburgh, UK
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Dominika Pankanin
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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Kenneth Weke
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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Alexander Laird
3Urology Department, Western General Hospital, NHS Lothian, Edinburgh, UK
4Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
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Christophe Battail
5CEA, Université Grenoble Alpes, INSERM, IRIG, Laboratoire Biosanté UMR1292, Grenoble, France
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Fabio Massimo Zanzotto
6Department of Enterprise Engineering, University of Rome “Tor Vergata”, Rome, Italy
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Catia Pesquita
7LASIGE, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
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Håkan Axelson
8Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden
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Ajitha Rajan
2School of Informatics, University of Edinburgh, Edinburgh, UK
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David J. Harrison
9School of Medicine, University of St Andrews, St Andrews, UK
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Aleksander Palkowski
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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Maciej Pawlik
10Academic Computer Centre CYFRONET, AGH University of Science and Technology, Cracow, Poland
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Maciej Parys
11Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Edinburgh, UK
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Robert O’Neill
12Cambridge Oesophagogastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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Paul M. Brennan
13Translational Neurosurgery, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
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Stefan Symeonides
4Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
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David R. Goodlett
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
14Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada
15University of Victoria Genome BC Proteome Centre, Victoria, Canada
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Kevin Litchfield
16Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK
17Tumour Immunogenomics and Immunosurveillance Laboratory, University College London Cancer Institute, London, UK
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Robin Fahraeus
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
18Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris 7, Paris, France
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Ted R. Hupp
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
4Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
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Sachin Kote
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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  • For correspondence: javier.alfaro@proteogenomics.ca sachin.kote@ug.edu.pl
Javier A. Alfaro
1International Centre for Cancer Vaccine Science, University of Gdansk, Gdansk, Poland
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  • ORCID record for Javier A. Alfaro
  • For correspondence: javier.alfaro@proteogenomics.ca sachin.kote@ug.edu.pl
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Abstract

A longstanding disconnect between the growing number of MHC Class I immunopeptidomic studies and genomic medicine hinders cancer vaccine design. We develop COD-dipp to genomically map the full spectrum of detected canonical and non-canonical (non-exonic) MHC Class I antigens from 26 cancer studies. We demonstrate that patient mutations in regions overlapping physically identified antigens better predict immunotherapy response when compared to neoantigen predictions. We suggest a vaccine design approach using 140,966 highly immune-visible regions of the genome annotated by their expression and haplotype frequency in the human population. These regions tend to be highly conserved, mutated in cancer and harbor 7.8 times more immunogenicity. Intersecting pan-cancer mutations with these immune surveilled regions revealed a potential to create off-the-shelf multi-epitope vaccines against public neoantigens. Here we release COD-dipp, a cancer vaccine toolkit as a web-application (https://www.proteogenomics.ca/COD-dipp) and open-source high-throughput resource.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • 1. remove 'upon peer review' from the abstract. 2. Update the web-application link.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 20, 2022.
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A comprehensive library of canonical and non-canonical MHC class I antigens for cancer vaccine development
Georges Bedran, Tongjie Wang, Dominika Pankanin, Kenneth Weke, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Catia Pesquita, Håkan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Palkowski, Maciej Pawlik, Maciej Parys, Robert O’Neill, Paul M. Brennan, Stefan Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fahraeus, Ted R. Hupp, Sachin Kote, Javier A. Alfaro
bioRxiv 2022.01.13.475872; doi: https://doi.org/10.1101/2022.01.13.475872
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A comprehensive library of canonical and non-canonical MHC class I antigens for cancer vaccine development
Georges Bedran, Tongjie Wang, Dominika Pankanin, Kenneth Weke, Alexander Laird, Christophe Battail, Fabio Massimo Zanzotto, Catia Pesquita, Håkan Axelson, Ajitha Rajan, David J. Harrison, Aleksander Palkowski, Maciej Pawlik, Maciej Parys, Robert O’Neill, Paul M. Brennan, Stefan Symeonides, David R. Goodlett, Kevin Litchfield, Robin Fahraeus, Ted R. Hupp, Sachin Kote, Javier A. Alfaro
bioRxiv 2022.01.13.475872; doi: https://doi.org/10.1101/2022.01.13.475872

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