STINGRay therapy combines innate and adaptive immunity to control tumors

The experiments described in this proposal focus on pancreatic cancer, a prime example of negative immune biology at work, and not coincidentally one of the most lethal malignancies with a five-year survival rate of less than 5%; a crucial target for effective therapy. We propose that lessons learned in pancreatic cancer will be highly translatable to cancers where many patients share a similar combination of issues, including hepatocellular carcinoma, colorectal cancer and breast cancer. We propose that by using a molecule engineered to mimic an infection and combining it with radiation, we can not only keep the tumor-fighting immune response turned on at the treatment site, but can also enhance the immune system's ability to seek and destroy all cancerous cells in the body. We term this powerful combination STINGRay. Our research addresses three specific questions using mouse models of disease to better understand this therapy and move it forward towards use in pancreatic cancer patients. First, we will identify the specific immune cell type that is responsible for tumor cell death when our therapy is used. Secondly, we will determine if we can improve control of distant disease beyond the treated primary tumor by protecting immune cells from signals that inactivate them. Thirdly, we will determine if our therapeutic agent can be given systemically in combination with high dose radiation or chemotherapy to control tumors, which would dramatically increase the practicality of scope of application of this novel therapy.