title: The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection.
abstract: Many strategies have been used to enhance the peptide vaccine immune response and to establish therapeutic benefits. This includes the utilization of cytokines to improve antigen presentation or enhance T cell response. Here, we have tested the combination of GM-CSF and IL-2 as locally administered adjuvant to enhance the immune response to the HPV16 E7 peptide. Female C57BL/6 mice were immunized intradermally with a 9-mer HPV16 E7 peptide (aa: 49-57) alone, or in combination with GM-CSF, IL-2, or both cytokines. Specific immune responses were measured by ELISA and Chromium-Release Assays. Furthermore, therapeutic effects of these vaccines and long term tumor protection were assessed in mice bearing established tumors. We showed that GM-CSF and IL-2, when co-administered locally in an emulsion with peptide, exert a synergistic effect in enhancing the immune response to the antigen. This combination induced higher CTL and cytokine release responses and did not increase the T(reg) population. Therapeutic intervention with this synergistic combination led to a complete response of established tumors. Furthermore, this combination induced a memory response which protected mice against subsequent additional tumor challenge. We identified a new vaccine adjuvant, a local combination of GM-CSF and IL-2, which is synergistic in enhancing peptide specific immune response through local effect without increasing T(reg) cells. This immune response was found to be long lasting and protective in tumor bearing mice.
authors.affiliation: Cancer Vaccine Section, Vaccine Branch, NCI, NIH, Bethesda, MD, United States.
authors.forename: Antoun
authors.initials: A
authors.lastname: Toubaji
authors.forename: Sarah
authors.initials: S
authors.lastname: Hill
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: Jiahua
authors.initials: J
authors.lastname: Qian
authors.forename: Tamara
authors.initials: T
authors.lastname: Floyd
authors.forename: R Mark
authors.initials: RM
authors.lastname: Simpson
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
mesh_terms: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002460:Cell Line; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000276:immunology; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D019496:Cancer Vaccines; D007376:Interleukin-2; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D022223:Vaccines, Subunit; C059731:oncogene protein E7, Human papillomavirus type 16; D016178:Granulocyte-Macrophage Colony-Stimulating Factor