title: Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor.
abstract: OBJECTIVE
  To evaluate CD4(+) helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT).
  
  
  METHODS
  To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4(+) helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201-positive B16 melanoma that express TERT.
  
  
  RESULTS
  The presence of a high number of UCP-specific CD4(+) T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4(+) T(H)1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8(+) T cells.
  
  
  CONCLUSIONS
  Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers.
authors.affiliation: INSERM, UMR1098, Université de Franche-Comté, EFS Bourgogne Franche-Comté, CHU Besançon, Oncologie médicale, Besançon, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Dosset
authors.forename: Yann
authors.initials: Y
authors.lastname: Godet
authors.forename: Charline
authors.initials: C
authors.lastname: Vauchy
authors.forename: Laurent
authors.initials: L
authors.lastname: Beziaud
authors.forename: Yu Chun
authors.initials: YC
authors.lastname: Lone
authors.forename: Christine
authors.initials: C
authors.lastname: Sedlik
authors.forename: Christelle
authors.initials: C
authors.lastname: Liard
authors.forename: Emeline
authors.initials: E
authors.lastname: Levionnois
authors.forename: Bertrand
authors.initials: B
authors.lastname: Clerc
authors.forename: Federico
authors.initials: F
authors.lastname: Sandoval
authors.forename: Etienne
authors.initials: E
authors.lastname: Daguindau
authors.forename: Simon
authors.initials: S
authors.lastname: Wain-Hobson
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: Pierre
authors.initials: P
authors.lastname: Langlade-Demoyen
authors.forename: Christophe
authors.initials: C
authors.lastname: Borg
authors.forename: Olivier
authors.initials: O
authors.lastname: Adotévi
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology; D019098:Telomerase / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; C509186:TERT protein, human; D019098:Telomerase