We focus our studies on identification of therapeutic targets among signaling molecules which are involved in tumor-promoting inflammation. Our two-step immunotherapeutic strategy is first to disarm tumor defense systems, and then to activate immune attack from within.
Fighting cancer by activating immune system to search and destroy tumor cells with high precision could overcome the problem of serious side-effects observed after conventional cancer treatments. Recent advances in the understanding interactions between tumor and immune system identified that immune cells accumulated within tumor tissue are essential therapeutic targets for cancer immunotherapy. Dysfunctional immune cell populations within the tumor microenvironment secrete growth factors, promote blood vessel formation and disarm the immune system. Targeting immune cells in tumors poses problems due to the lack of specific therapeutics. We previously developed a novel reagent, CpG-siRNA molecules that allow for specific receptor-mediated delivery of the therapeutic agent (siRNA) into certain immune cell populations. We used CpG-siRNAs to block function of tumor-supporting immune cells, thereby generating potent antitumor immune responses in mice. Our recent studies suggest that the same strategy could restore the antitumor immune responses in cancer patients. Moreover, we used CpG-siRNAs to block oncogenic signaling and induce cell death in several types of human blood cancers, including acute myeloid leukemia (AML). We currently optimize CpG-siRNAs for use against metastatic tumors and multiple gene targets, what should generate novel, more effective and safer therapeutics, expanding treatment options for the benefit of cancer patients.