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In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
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Published on: February 27, 2019

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

Daniel E Speiser1, Petra Baumgaertner, Verena Voelter

  • 1Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research and University of Lausanne, and Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, 1001 Lausanne, Switzerland. daniel.speiser@hospvd.ch

Proceedings of the National Academy of Sciences of the United States of America
|March 6, 2008
PubMed

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.

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