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Unbiased analysis of all possible neoepitopes of MC38-FABF tumor reveals a new universe of cancer neoepitopes with unexpected properties

Mariam M George, Cory A Brennick, Marmar M Moussa, Adam T Hagymasi, Sahar Al Seesi, Tatiana V Shcheglova, Ryan P Englander, Grant L.J Keller, Jeremy L Balsbaugh, Brian M Baker, Ion I. Mandoiu and Pramod K Srivastava
J Immunol May 1, 2020, 204 (1 Supplement) 239.18;
Mariam M George
1University of Connecticut, Health Center
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Cory A Brennick
1University of Connecticut, Health Center
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Marmar M Moussa
1University of Connecticut, Health Center
2Department of Computer Sciences, University of Connecticut
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Adam T Hagymasi
1University of Connecticut, Health Center
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Sahar Al Seesi
3Smith college, Northampton, MA
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Tatiana V Shcheglova
1University of Connecticut, Health Center
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Ryan P Englander
1University of Connecticut, Health Center
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Grant L.J Keller
4University of Notre Dame
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Jeremy L Balsbaugh
5University of Connecticut
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Brian M Baker
4University of Notre Dame
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Ion I. Mandoiu
2Department of Computer Sciences, University of Connecticut
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Pramod K Srivastava
1University of Connecticut, Health Center
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Abstract

Cancer neoepitopes are the only truly tumor-specific antigens and therefore, the most suitable as cancer vaccines. Current methods to predict neoepitopes, based on studies of viral epitopes, emphasize high affinity MHC-peptide interactions. Increasing evidence in human and murine models indicates that the present neoepitope prediction methods are mostly inaccurate in predicting true MHC I-restricted cancer neoepitopes. Here, in a completely unbiased approach, all possible neoepitopes in a mouse tumor model were tested for their ability to mediate tumor rejection and also CD8+ T cell responses. These studies show that the true tumor rejecting neoepitopes have different properties from those of viral epitopes. Further, CD8+ T cell responses elicited by these neoepitopes possess a more plastic chromatin phenotype with stem-like properties that is known to be associated with anti-viral and anti-tumor immune responses. Such cancer neoepitopes can be exploited for generation of personalized cancer vaccines.

  • Copyright © 2020 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 204, Issue 1 Supplement
1 May 2020
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Unbiased analysis of all possible neoepitopes of MC38-FABF tumor reveals a new universe of cancer neoepitopes with unexpected properties
Mariam M George, Cory A Brennick, Marmar M Moussa, Adam T Hagymasi, Sahar Al Seesi, Tatiana V Shcheglova, Ryan P Englander, Grant L.J Keller, Jeremy L Balsbaugh, Brian M Baker, Ion I. Mandoiu, Pramod K Srivastava
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 239.18;

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Unbiased analysis of all possible neoepitopes of MC38-FABF tumor reveals a new universe of cancer neoepitopes with unexpected properties
Mariam M George, Cory A Brennick, Marmar M Moussa, Adam T Hagymasi, Sahar Al Seesi, Tatiana V Shcheglova, Ryan P Englander, Grant L.J Keller, Jeremy L Balsbaugh, Brian M Baker, Ion I. Mandoiu, Pramod K Srivastava
The Journal of Immunology May 1, 2020, 204 (1 Supplement) 239.18;
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Print ISSN 0022-1767        Online ISSN 1550-6606