Associate Professor, Bioengineering
University of Southern California
Focused ultrasound (FUS) can deliver energy safely and noninvasively into tissues at depths of centimeters. We show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumors can be reversibly controlled by the heat generated by short pulses of FUS via a CAR cassette under the control of a promoter for the heat-shock protein. In mouse tumor models, locally injected T cells with the inducible CAR and activated via FUS guided by magnetic resonance imaging (MRI) mitigated on-target off-tumor activity and enhanced the suppression of tumor growth, compared with the performance of standard CAR-T cells. Integrated with CRISPR, FUS was also be applied to modulate the genetics and epigenetics of tumor cells, which facilitated and enhanced the efficacy of the CAR T immunotherapy. Therefore, acoustogenetic control of tumor cells and CAR T by FUS may facilitate the design of safer cell therapies.