The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection

Antoun Toubaji, Sarah Hill, Masaki Terabe, Jiahua Qian, Tamara Floyd, R. Mark Simpson, Jay A. Berzofsky, Samir N. Khleif

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 Treg 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 Treg cells. This immune response was found to be long lasting and protective in tumor bearing mice.

Original languageEnglish (US)
Pages (from-to)5882-5891
Number of pages10
JournalVaccine
Volume25
Issue number31
DOIs
StatePublished - Aug 1 2007

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Subunit Vaccines
subunit vaccines
Granulocyte-Macrophage Colony-Stimulating Factor
interleukin-2
adjuvants
Interleukin-2
immune response
neoplasms
peptides
Neoplasms
cytokines
mice
therapeutics
Peptides
Cytokines
vaccine adjuvants
antigen presentation
Vaccines
chromium
emulsions

Keywords

  • Adjuvant
  • GM-CSF
  • IL-2
  • Immunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection. / Toubaji, Antoun; Hill, Sarah; Terabe, Masaki; Qian, Jiahua; Floyd, Tamara; Simpson, R. Mark; Berzofsky, Jay A.; Khleif, Samir N.

In: Vaccine, Vol. 25, No. 31, 01.08.2007, p. 5882-5891.

Research output: Contribution to journalArticle

Toubaji, A, Hill, S, Terabe, M, Qian, J, Floyd, T, Simpson, RM, Berzofsky, JA & Khleif, SN 2007, 'The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection', Vaccine, vol. 25, no. 31, pp. 5882-5891. https://doi.org/10.1016/j.vaccine.2007.05.040
Toubaji, Antoun ; Hill, Sarah ; Terabe, Masaki ; Qian, Jiahua ; Floyd, Tamara ; Simpson, R. Mark ; Berzofsky, Jay A. ; Khleif, Samir N. / The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection. In: Vaccine. 2007 ; Vol. 25, No. 31. pp. 5882-5891.
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