Synthetic Biology in Chimeric Antigen Receptor T (CAR T) Cell Engineering

Synthetic biology is a novel interdisciplinary research area following engineering principles to redesign and construct biological systems for useful purposes. As one of the most notable clinically relevant application of synthetic biology, chimeric antigen receptor (CAR) T cells have demonstrated tremendous success for the treatment of advanced hematological malignancies in recent years. However, various unsolved obstacles limit the widespread application of CAR T cell therapies, including treatment-associated toxicities, antigen heterogeneity, antigen escape, poor CAR T cell persistence and expansion, and particularly inefficient homing, infiltrating into, and surviving within solid tumors. Accordingly, to improve therapeutic efficacy and minimize side effects, innovative CAR design becomes urgently necessary, and researchers are developing numerous methods to overcome the limitations. Here we summarize currently available bioengineering strategies and discuss the future development from a viewpoint of synthetic biology.