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 language | English |
|---|---|
| Pages (from-to) | 1983-1990 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 175 |
| Issue number | 3 |
| Publication status | Published - Aug 1 2005 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - The TLR7 agonist imiquimod enhances the anti-melanoma effects of a recombinant Listeria monocytogenes vaccine
AU - Craft, Noah
AU - Bruhn, Kevin W.
AU - Nguyen, Bidong D.
AU - Prins, Robert
AU - Lin, Jia Wei
AU - Liau, Linda M.
AU - Miller, Jeffery F.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=22544433125&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22544433125&partnerID=8YFLogxK
M3 - Article
C2 - 16034143
AN - SCOPUS:22544433125
VL - 175
SP - 1983
EP - 1990
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -