title: Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors.
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.
  
  
  CONCLUSIONS
  The combination of agonists targeting TLRs 7/8 and 9 represents a significant improvement in cancer immunotherapy.
authors: Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick MD 21702, USA.
authors: By Gan
authors: BG
authors: Zhao
authors: 3M Drug Delivery Systems Division, St. Paul MN 55144, USA.
authors: John P
authors: JP
authors: Vasilakos
authors: Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick MD 21702, USA.
authors: Debra
authors: D
authors: Tross
authors: 3M Drug Delivery Systems Division, St. Paul MN 55144, USA.
authors: Dmitri
authors: D
authors: Smirnov
authors: Cancer and Inflammation Program, National Cancer Institute, NIH, Frederick MD 21702, USA.
authors: Dennis M
authors: DM
authors: Klinman
keywords: Cancer; CpG ODN; Innate immunity; TLR agonists; Therapy