Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen

Daniel E. Speiser, Petra Baumgaertner, Verena Voelter, Estelle Devevre, Catherine Barbey, Nathalie Rufer, Pedro Romero

Research output: Contribution to journalArticle

103 Scopus citations

Abstract

Human cancer vaccines are often prepared with altered "analog" or "heteroclitic" antigens that have been optimized for HLA class I binding, resulting in enhanced immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful vaccine adjuvants and demonstrate the induction of high T cell frequencies in melanoma patients, despite the use of natural (unmodified) tumor antigenic peptide. Compared with vaccination with analog peptide, natural peptide induced T cell frequencies that were approximately twofold lower. However, T cells showed superior tumor reactivity because of (i) increased functional avidity for natural antigen and (ii) enhancement of T cell activation and effector function. Thus, novel vaccine formulations comprising potent immune stimulators may allow to circumvent the need for modified antigens and can induce highly functional T cells with precise antigen specificity.

Original languageEnglish (US)
Pages (from-to)3849-3854
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number10
DOIs
StatePublished - Mar 25 2008
Externally publishedYes

Keywords

  • Analog peptides
  • CD8 T cell specificity
  • CpG oligodeoxynucleotides
  • Immunotherapy
  • Toll-like receptor 9

ASJC Scopus subject areas

  • General

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