Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity than altered antigen.
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.
Speiser
Daniel E
DE
Division 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
Baumgaertner
Petra
P
Voelter
Verena
V
Devevre
Estelle
E
Barbey
Catherine
C
Rufer
Nathalie
N
Romero
Pedro
P
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002999:Clone Cells; D000939:Epitopes / Q000276:immunology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D058965:MART-1 Antigen; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D014611:Vaccination
D000951:Antigens, Neoplasm; D001324:Autoantigens; D019496:Cancer Vaccines; D000939:Epitopes; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes