Precision Tools in Immuno-Oncology: Synthetic Gene Circuits for Cancer Immunotherapy

Engineered mammalian cells for medical purposes are becoming a clinically relevant reality thanks to advances in synthetic biology that allow enhanced reliability and safety of cell-based therapies. However, their application is still hampered by challenges including time-consuming design-and-test cycle iterations and costs. For example, in the field of cancer immunotherapy, CAR-T cells targeting CD19 have already been clinically approved to treat several types of leukemia, but their use in the context of solid tumors is still quite inefficient, with additional issues related to the adequate quality control for clinical use. These limitations can be overtaken by innovative bioengineering approaches currently in development. Here we present an overview of recent synthetic biology strategies for mammalian cell therapies, with a special focus on the genetic engineering improvements on CAR-T cells, discussing scenarios for the next generation of genetic circuits for cancer immunotherapy.