Wu, Jusiak, and Lu review several synthetic biology approaches to bring engineering principles (logic gating, system design, user-controlled inputs) to cancer therapies. Cell-based therapies could use logical protein recognition programming, which requires the presence and/or absence of multiple antigens, to prevent off-target/systemic toxicities. DNA and RNA gene circuits, delivered to tumor cells or the TME, could similarly be programmed to respond to multiple inputs prior to activation and payload deployment. Challenges to these approaches include robust manufacturing practices and optimized delivery methods.
Engineered immune-cell-based cancer therapies have demonstrated robust efficacy in B cell malignancies, but challenges such as the lack of ideal targetable tumour antigens, tumour-mediated immunosuppression and severe toxicity still hinder their therapeutic efficacy and broad applicability. Synthetic biology can be used to overcome these challenges and create more robust, effective adaptive therapies that enable the specific targeting of cancer cells while sparing healthy cells. In this Progress article, we review recently developed gene circuit therapies for cancer using immune cells, nucleic acids and bacteria as chassis. We conclude by discussing outstanding challenges and future directions for realizing these gene circuit therapies in the clinic.