Abstract | BACKGROUND: The TLR7/8 agonist 3M-052 and the TLR9 agonist CpG ODN both trigger innate immune responses that support the induction of tumor-specific immunity. Previous studies showed that these agonists used individually could improve the survival of mice challenged with small tumors but were of limited therapeutic benefit against large/advanced tumors. METHODS: Normal mice were challenged with syngeneic tumors. Once these tumors reached clinically detectable size (500-800 mm(3)) they were treated by intra-tumoral injection with 3M-052 and/or CpG ODN. Anti- tumor immunity and tumor growth were evaluated. RESULTS: The co-delivery of agonists targeting TLRs 7, 8 and 9 increased the number and tumoricidal activity of tumor infiltrating CTL and NK cells while reducing the frequency of immunosuppressive MDSC. The combination of 3M-052 plus CpG ODN (but not each agent alone) eradicated large primary tumors and established long-term protective immunity. CONCLUSION: The combination of agonists targeting TLRs 7/8 and 9 represents a significant improvement in cancer immunotherapy.
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Authors | By Gan Zhao, John P Vasilakos, Debra Tross, Dmitri Smirnov, Dennis M Klinman |
Journal | Journal for immunotherapy of cancer
(J Immunother Cancer)
Vol. 2
Pg. 12
( 2014)
ISSN: 2051-1426 [Print] England |
PMID | 24982761
(Publication Type: Journal Article)
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