Cell-based therapies are an exciting frontier in medicine. This field is built on a simple premise—cells can be engineered to recognize and treat various human diseases. The paradigm of cell-based therapy uses biosensors to interrogate a cell’s environment and distinguish disease from health, intracellular signaling pathways and genetic circuitry to process, integrate, and interpret this information, and effector functions to enact a therapeutic response against the disease. Best exemplified at present by chimeric antigen receptor modified T cells, which are programmed to patrol the body and to seek out and destroy tumor cells, cellular therapeutics hold promise for treating cancer and many other pathologies. Though several cell-based therapies have gained FDA approval in recent years for clinical use against hematologic malignancies, the reach of cell-based therapies is limited by many factors, including the availability of fundamental technologies that could enable us to target the cells against a broad range of diseases. This thesis aims to address this problem through two overarching efforts:(I) developing fundamental technologies for cell-based biosensors and therapeutics and (II) translating these cell-based devices for clinical applications.