Engineering cell-based therapies to interface robustly with host physiology.
Engineered cell-based therapies comprise a rapidly growing clinical technology for treating disease by leveraging the natural capabilities of cells, including migration, information transduction, and biosynthesis and secretion. There now exists a substantial portfolio of intracellular and extracellular sensors that enable bioengineers to program cells to execute defined responses to specific changes in state or environmental cues. As our capability to construct more sophisticated cellular programs increases, assessing and improving the degree to which cell-based therapies perform as desired in vivo will become an increasingly important consideration and opportunity for technological advancement. In this review, we seek to describe both current capabilities and potential needs for building cell-based therapies that interface with host physiology in a manner that is robust - a phrase we use in this context to describe the achievement of therapeutic efficacy across a range of patients and implementations. We first review the portfolio of sensors and outputs currently available for use in cell-based therapies by highlighting key advancements and current gaps. Then, we propose a conceptual framework for evaluating and pursuing robust clinical performance of engineered cell-based therapies.
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd., Evanston, IL 60208, United States.
Kelly A
KA
Schwarz
Department of Chemical and Biological Engineering, Northwestern University, 2145 Sheridan Rd., Evanston, IL 60208, United States; Chemistry of Life Processes Institute, Northwestern University, 2170 Campus Dr., Evanston, IL 60208, United States; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 675 N. St. Clair, Chicago, IL 60611, United States. Electronic address: j-leonard@u.northwestern.edu.
Joshua N
JN
Leonard
D000818:Animals; D060846:Cell Engineering; D064987:Cell- and Tissue-Based Therapy; D006801:Humans
Biosensors; Cell-based therapies; Gene circuits; Mammalian synthetic biology