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Reprogramming Tumor Immunogenicity with STING-Activating Nanoparticles

John T. Wilson, PhD

Dr. Wilson is an assistant professor in the Department of Chemical and Biomolecular Engineering at Vanderbilt University in Nashville. His SU2C Innovative Research Grant project, awarded in 2017, is titled “Reprogramming Tumor Immunogenicity with STING-Activating Nanoparticles.”

Cancer immunotherapy seeks to harness a patient’s own immune system to specifically destroy cancer cells throughout the body with minimal toxicity to surrounding tissue, while also training the immune system to “remember” how to kill cancer cells if they return. Recently approved checkpoint inhibitors have transformed the treatment of an increasing number of different types of cancer by reactivating T cells that recognize cancer cells. However, many patients still do not completely respond to this type of treatment. There are two primary and intertwined reasons for this: 1) patients have nonimmunogenic or “cold” tumors that are able to evade recognition by T cells, and 2) patients lack a sufficient number of the correct type of antitumor T cells necessary to efficiently destroy tumors. The aim of this research is to develop a safe and effective approach for increasing antitumor T cell responses within tumors and, by doing so, improve the effectiveness of checkpoint blockade immunotherapy. To achieve this goal, Dr. Wilson plans to develop “smart” nanoparticles coated with a small molecule that will act on the inflammatory pathway to turn “cold” tumors into “hot” ones, becoming recognizable by the immune system. Another complementary aspect of this project is to coat the nanoparticles with tumor antigens as well to better train T cells to recognize and attack cancer cells. Overall, this innovative proposal combines multiple approaches, using state-of-the art bioengineering, mouse tumor models, and a series of advanced proteomics and cell biology tools, and offers the potential to positively impact patient outcomes by developing a versatile, safe, and scalable drug-delivery platform for personalized immunotherapy.