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Cancer Immunology Research
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Research Articles

Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors

Greta Garrido, Brett Schrand, Agata Levay, Ailem Rabasa, Anthony Ferrantella, Diane M. Da Silva, Francesca D'Eramo, Koen A. Marijt, Zhuoran Zhang, Deukwoo Kwon, Marcin Kortylewski, W. Martin Kast, Vikas Dudeja, Thorbald van Hall and Eli Gilboa
Greta Garrido
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
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Brett Schrand
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
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Agata Levay
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
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Ailem Rabasa
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
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Anthony Ferrantella
2Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
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  • ORCID record for Anthony Ferrantella
Diane M. Da Silva
3Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Francesca D'Eramo
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
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Koen A. Marijt
4Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands.
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  • ORCID record for Koen A. Marijt
Zhuoran Zhang
5Department of Immuno-Oncology, Beckman Research Institute, City of Hope Medical Center, Duarte, California.
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  • ORCID record for Zhuoran Zhang
Deukwoo Kwon
6Department of Public Health Sciences, University of Miami, Miller School of Medicine, Miami, Florida.
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Marcin Kortylewski
5Department of Immuno-Oncology, Beckman Research Institute, City of Hope Medical Center, Duarte, California.
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W. Martin Kast
3Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
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Vikas Dudeja
2Department of Surgery, University of Miami, Miller School of Medicine, Miami, Florida.
7Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida.
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Thorbald van Hall
4Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, the Netherlands.
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Eli Gilboa
1Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida.
7Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, Florida.
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  • For correspondence: egilboa@med.miami.edu
DOI: 10.1158/2326-6066.CIR-20-0020 Published July 2020
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Abstract

Vaccination of patients against neoantigens expressed in concurrent tumors, recurrent tumors, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP downregulation–induced antigens was more effective than vaccination against mutation-derived neoantigens, was devoid of measurable toxicity, and inhibited the growth of concurrent and future tumors in models of recurrence and premalignant disease. Human CD8+ T cells stimulated with TAPlow dendritic cells elicited a polyclonal T-cell response that recognized tumor cells with experimentally reduced TAP expression. Vaccination against TAP downregulation–induced antigens overcomes the main limitations of vaccinating against mostly unique tumor-resident neoantigens and could represent a simpler vaccination strategy that will be applicable to most patients with cancer.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2020;8:856–68

  • Received January 9, 2020.
  • Revision received February 25, 2020.
  • Accepted April 8, 2020.
  • Published first April 15, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Immunology Research: 8 (7)
July 2020
Volume 8, Issue 7
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Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors
Greta Garrido, Brett Schrand, Agata Levay, Ailem Rabasa, Anthony Ferrantella, Diane M. Da Silva, Francesca D'Eramo, Koen A. Marijt, Zhuoran Zhang, Deukwoo Kwon, Marcin Kortylewski, W. Martin Kast, Vikas Dudeja, Thorbald van Hall and Eli Gilboa
Cancer Immunol Res July 1 2020 (8) (7) 856-868; DOI: 10.1158/2326-6066.CIR-20-0020

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Vaccination against Nonmutated Neoantigens Induced in Recurrent and Future Tumors
Greta Garrido, Brett Schrand, Agata Levay, Ailem Rabasa, Anthony Ferrantella, Diane M. Da Silva, Francesca D'Eramo, Koen A. Marijt, Zhuoran Zhang, Deukwoo Kwon, Marcin Kortylewski, W. Martin Kast, Vikas Dudeja, Thorbald van Hall and Eli Gilboa
Cancer Immunol Res July 1 2020 (8) (7) 856-868; DOI: 10.1158/2326-6066.CIR-20-0020
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