The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine.
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.
Craft
Noah
N
Division of Dermatology, Department of Medicine and Specialty Training and Advanced Research Program, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1747, USA. ncraft@ucla.edu
Bruhn
Kevin W
KW
Nguyen
Bidong D
BD
Prins
Robert
R
Lin
Jia Wei
JW
Liau
Linda M
LM
Miller
Jeffery F
JF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D004357:Drug Synergism; D005260:Female; D000077271:Imiquimod; D007279:Injections, Subcutaneous; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011956:Receptors, Cell Surface / Q000819:agonists*; D051199:Toll-Like Receptor 7; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D014614:Vaccines, Synthetic; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D000077271:Imiquimod