Combinatorial immunotherapy with RIG-I and TLR8 ligands in humanized mice

Immunotherapy of cancer with checkpoint inhibitors (CPI) has been a tremendous success for the treatment of cancer in the recent years. Unfortunately, not all patients show responses to this form of therapy. “Hot” tumors, which are defined by a T-cell inflamed microenvironment, seem to respond to CPI therapy much more frequently than “cold” tumors, where no prior autonomous activation of the immune system has taken place
Thus, the induction of T-cell driven inflammation would likely enhance response rates to CPI and could be achieved by stimulation of the innate immune system by ligands of pattern recognition receptors. Especially the combination of RIG-I ligands, which are strong inducers of type I interferons, with TLR8 ligands, which can activate the IL12p70 and IFNg pathways may yield improved results. This projects therefore aims at the development of combinatorial TLR8 RIG-I immunotherapies and the investigation of the effects of these ligands on the tumor microenvironment.