Article: article from journal or magazin.
Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen
Proceedings of the National Academy of Sciences of the United States of America
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
Amino Acid Sequence , Antigens,Neoplasm , Autoantigens , biosynthesis , Cancer Vaccines , CD8-Positive T-Lymphocytes , chemistry , Clone Cells , Epitopes , Granzymes , Humans , immunology , Interferon-gamma , Lymphocyte Activation , Melanoma , metabolism , Molecular Sequence Data , Neoplasm Proteins , Neoplasms , Patients , Peptides , Perforin , Proteins , Switzerland , Vaccination
Web of science
Last modification date