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J Immunother Cancer. 2014 May 13;2:12. doi: 10.1186/2051-1426-2-12. eCollection 2014.

Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors.

Author information

1
Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick MD 21702, USA.
2
3M Drug Delivery Systems Division, St. Paul MN 55144, USA.

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.

KEYWORDS:

Cancer; CpG ODN; Innate immunity; TLR agonists; Therapy

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