The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine

Noah Craft, Kevin W. Bruhn, Bidong D. Nguyen, Robert Prins, Jia Wei Lin, Linda M. Liau, Jeffery F. Miller

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Activation of innate immune cells through TLR triggers immunomodulating events that enhance cell-mediated immunity, raising the possibility that ligands to these receptors might act as adjuvants in conjunction with T cell activating vaccines. In this report, topical imiquimod, a synthetic TLR7 agonist, significantly enhanced the protective antitumor effects of a live, recombinant listeria vaccine against murine melanoma. This tumor protective effect was not dependent on direct application to the tumor and was associated with an increase in tumor-associated and splenic dendritic cells. Additionally, the combination of imiquimod treatment with prior vaccination led to development of localized vitiligo. These findings indicate that activation of the innate immune system with TLR ligands stimulates dendritic cell activity resulting in a bypass of peripheral tolerance and enhanced antitumor activity. The results of these studies have broad implications for future designs of immunotherapeutic vaccines against tumors and the treatment of metastatic melanoma.

Original languageEnglish
Pages (from-to)1983-1990
Number of pages8
JournalJournal of Immunology
Volume175
Issue number3
Publication statusPublished - Aug 1 2005
Externally publishedYes

Fingerprint

imiquimod
Listeria monocytogenes
Melanoma
Vaccines
Dendritic Cells
Peripheral Tolerance
Ligands
Neoplasms
Vitiligo
Cancer Vaccines
Synthetic Vaccines
Listeria
Cellular Immunity
Immune System
Vaccination
T-Lymphocytes
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Craft, N., Bruhn, K. W., Nguyen, B. D., Prins, R., Lin, J. W., Liau, L. M., & Miller, J. F. (2005). The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine. Journal of Immunology, 175(3), 1983-1990.

The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine. / Craft, Noah; Bruhn, Kevin W.; Nguyen, Bidong D.; Prins, Robert; Lin, Jia Wei; Liau, Linda M.; Miller, Jeffery F.

In: Journal of Immunology, Vol. 175, No. 3, 01.08.2005, p. 1983-1990.

Research output: Contribution to journalArticle

Craft, N, Bruhn, KW, Nguyen, BD, Prins, R, Lin, JW, Liau, LM & Miller, JF 2005, 'The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine', Journal of Immunology, vol. 175, no. 3, pp. 1983-1990.
Craft, Noah ; Bruhn, Kevin W. ; Nguyen, Bidong D. ; Prins, Robert ; Lin, Jia Wei ; Liau, Linda M. ; Miller, Jeffery F. / The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine. In: Journal of Immunology. 2005 ; Vol. 175, No. 3. pp. 1983-1990.
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