TY - JOUR T1 - Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/2051-1426-2-12 VL - 2 IS - 1 SP - 12 AU - By Gan Zhao AU - John P Vasilakos AU - Debra Tross AU - Dmitri Smirnov AU - Dennis M Klinman Y1 - 2014/12/01 UR - http://jitc.bmj.com/content/2/1/12.abstract N2 - 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 mm3) 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.Abbreviations:CTLCytotoxic T cellDCDendritic cellMDSCMyeloid derived suppressor cellODNOligonucleotidePAMPPathogen-associated molecular patternTLRToll-like receptor. ER -