Ming-Ru Wu, MD, PhD, CLIP Investigator Dana-Farber Cancer Institute Area of Research: Ovarian Cancer Cancer immunotherapy has demonstrated great potential for treating cancer. However, challenges such as the lack of ideal targets, severe toxicity due to off-target interactions, and tumor-mediated immunosuppression are limiting the successful application of immunotherapies for a broad range of cancers. To overcome these challenges, Dr. Wu has developed a programmable “gene circuit” platform that enables the production of tumor-localized therapeutic payloads to recruit and activate immune cells: Tumor Immunotherapy by Gene-circuit Engineered Response (TIGER). These gene circuits can be delivered systemically, but are only turned on by the presence of the multiple cancer-specific transcriptions factors, minimizing the off-target effects on normal cells. When activated, it will force cancer cells to produce immune-boosting molecules. Dr. Wu has demonstrated that TIGER elicited a strong immune response and established long-lasting protection in mouse models of ovarian cancer. To apply this platform in the clinic, however, several advances are required, including the ability to efficiently identify the cancer-specific transcriptions factors in individual patients’ tumors as well to optimize the composition of the immune-boosting payloads and delivery methods. This proposal will focus on advancing these three aspects to facilitate clinical translation of TIGER to treat ovarian cancer and overcome existing barriers to effective immunotherapy. Projects and Grants Synthetic Immunomodulatory Gene Circuits for Ovarian Cancer Massachusetts Institute of Technology | Ovarian Cancer | 2020
