2019-06-25
Cancer immunotherapy has demonstrated robust efficacy in clinical trials, but challenges such as the lack of ideal targetable tumor antigens, severe toxicity, and tumor-mediated immunosuppression still limit its success. To overcome these challenges, I have designed a synthetic cancer-targeting gene circuit platform that enables a localized and robust combinatorial immunotherapy from within cancer cells: a Trojan horse-like approach. Once the circuits are introduced into cells, they will sense cancer-specific transcription factor activities, and trigger an effective combinatorial immunotherapy selectively from within cancer cells, while keeping normal cells unharmed. The circuit cured disseminated ovarian cancer in vivo in a mouse model. This platform can be adjusted to treat multiple cancer types and can potentially trigger any genetically-encodable immunomodulators as therapeutic outputs. Moreover, this gene circuit platform can be adapted to treat additional diseases exhibiting aberrant transcription factor activities, such as chronic metabolic diseases and autoimmune disorders.