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Cancer Immunol Res DOI:10.1158/2326-6066.CIR-13-0227

HLA-binding properties of tumor neoepitopes in humans.

Publication TypeJournal Article
Year of Publication2014
AuthorsFritsch, EF, Rajasagi, M, Ott, PA, Brusic, V, Hacohen, N, Wu, CJ
JournalCancer Immunol Res
Date Published2014 Jun
KeywordsAlgorithms, Antigens, Neoplasm, Cancer Vaccines, Epitopes, T-Lymphocyte, Histocompatibility Antigens Class I, Humans, Immunity, Cellular, Mutation, Missense, Neoplasms, T-Lymphocytes

Cancer genome sequencing has enabled the rapid identification of the complete repertoire of coding sequence mutations within a patient's tumor and facilitated their use as personalized immunogens. Although a variety of techniques are available to assist in the selection of mutation-defined epitopes to be included within the tumor vaccine, the ability of the peptide to bind to patient MHC is a key gateway to peptide presentation. With advances in the accuracy of predictive algorithms for MHC class I binding, choosing epitopes on the basis of predicted affinity provides a rapid and unbiased approach to epitope prioritization. We show herein the retrospective application of a prediction algorithm to a large set of bona fide T cell-defined mutated human tumor antigens that induced immune responses, most of which were associated with tumor regression or long-term disease stability. The results support the application of this approach for epitope selection and reveal informative features of these naturally occurring epitopes to aid in epitope prioritization for use in tumor vaccines.


Alternate JournalCancer Immunol Res
PubMed ID24894089
PubMed Central IDPMC4049249
Grant ListR01 CA155010 / CA / NCI NIH HHS / United States
R01 HL103532 / HL / NHLBI NIH HHS / United States
1R01CA155010-02 / CA / NCI NIH HHS / United States
R01 HL103532-03 / HL / NHLBI NIH HHS / United States