2022 breakthrough board scholar

RNA Guided Gene Editing to turn “cold” tumor environments to “hot”

Due to the successful implementation of targeted therapies and immunotherapy, 50% of melanoma patients with metastasized tumors live more than five years after diagnosis. Unfortunately, some patients show no response to immunotherapy and 80% of all patients fail to have a complete response. This variation in patient response to immunotherapy has led doctors to categorize tumor environments as either “hot” or “cold,” where “hot” tumor environments, indicated by attributes such as high levels of checkpoint proteins, are much more likely to have a favorable response. Many studies have suggested that activation of the cGAS-STING pathway primes tumor-specific T cells in the anti-cancer immune response. We have small molecules that promote the STING pathway.  However, in the absence of a mechanism that restricts this effect to tumors, targeting cGAS-STING may trigger system-wide side effects such as prolonged inflammation and autoimmune disorders.

Dr. Tang has developed a technology to selectively activate the cGAS-STING pathway in the tumor microenvironment, enabling efficient cancer recognition and clearance by immune cells, without affecting healthy tissues. Dr. Tang intends to prove that this platform, based on CRISPR gene editing and modulated by RNA, will have the ability to transform “cold” melanoma into “hot” melanoma.  This ability to boost innate immunity only at places where it is needed would provide a powerful therapeutic option.  Dr. Tang hopes to develop her platform into a treatment for melanoma that is customizable for individual patients and could both serve as a stand-alone therapy or be combined with existing immunotherapies.