title: Combination of the toll like receptor agonist and α-Galactosylceramide as an efficient adjuvant for cancer vaccine.
abstract: BACKGROUND
  DNA vaccines have emerged as an attractive approach for the generation of cytotoxic T lymphocytes (CTL). In our previous study, we found That Toll like receptor (TLR) ligands are promising candidates for the development of novel adjuvants for DNA vaccine. To improve the efficacy of DNA vaccine directed against human papillomavirus (HPV) tumors, we evaluated whether co-administration of a TLR4 ligand, monophosphoryl lipid A (MPL), and Natural Killer T Cell Ligand α-Galactosylceramide(α-GalCer) adjuvants with DNA vaccine would influence the anti-tumor efficacy of DNA vaccinations.
  
  
  METHODS
  We investigated the effectiveness of α-GalCer and MPL combination as an adjuvant with an HPV-16 E7 DNA vaccine to enhance antitumor immune responses.
  
  
  RESULTS
  By using adjuvant combination for a DNA vaccine, we found that the levels of lymphocyte proliferation, CTL activity, IFN- γ, IL-4 and IL-12 responses, and tumor protection against TC-1 cells were significantly increased compared to the DNA vaccine with individual adjuvants. In addition, inhibition of IL-18 signaling during vaccination decreased IFN-γ responses and tumor protection, and that this inhibition suggested stimulatory role of IL-18 in adjuvant effects of α-GalCer and MPL combination.
  
  
  CONCLUSIONS
  The strong adjuvanticity associated with α-GalCer/MPL combination may to be an important tool in the development of novel and strong cancer immunotherapy.
authors.affiliation: Infectious Diseases Research Center, Department of Microbiology, Golestan University of Medical Sciences, POBox: 49175-1141, Gorgan, Iran.
authors.forename: Fateme
authors.initials: F
authors.lastname: Gableh
authors.affiliation: Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Saeidi
authors.affiliation: Guilan Science and Research Branch, Islamic Azad University, Rasht, Iran.
authors.forename: Shaghayegh
authors.initials: S
authors.lastname: Hemati
authors.affiliation: Department of microbiology, Islamic Azad University, Shiraz branch, Shiraz, Iran.
authors.forename: Kasra
authors.initials: K
authors.lastname: Hamdi
authors.affiliation: Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Hoorieh
authors.initials: H
authors.lastname: Soleimanjahi
authors.affiliation: Shefa Neuroscience Research Center, Tehran, Iran.|Epilepsy Research Center, Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Robert-Koch-Strasse, Münster, Germany.|Klinik und Poliklinik für Neurochirurgie, Department of Neurology, Westfälische Wilhelms-Universität Münster, Münster, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Gorji
authors.affiliation: Infectious Diseases Research Center, Department of Microbiology, Golestan University of Medical Sciences, POBox: 49175-1141, Gorgan, Iran. ghaem_amir@yahoo.com.|Shefa Neuroscience Research Center, Tehran, Iran. ghaem_amir@yahoo.com.|Department of Virology, Pasteur Institute of Iran, Tehran, Iran. ghaem_amir@yahoo.com.
authors.forename: Amir
authors.initials: A
authors.lastname: Ghaemi
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D005260:Female; D005699:Galactosylceramides / Q000276:immunology / Q000494:pharmacology*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D005699:Galactosylceramides; D008050:Lipid A; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019444:Vaccines, DNA; C493154:alpha-galactosylceramide; C048436:monophosphoryl lipid A
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