Harnessing closed-loop MRgFUS hyperthermia and thermal bioswitches for spatiotemporal regulation of immunotherapy.

In collaboration with the Kwong Lab, our laboratory pioneered a closed-loop sonothermogenetic strategy for the remote, spatiotemporal regulation of engineered chimeric antigen receptor (CAR) T cells deep within the brain (BiorXiv)). Using transcranial MR-guided focused ultrasound (MRgFUS) with real-time thermometry feedback, we developed PID-based control frameworks that maintain rapid, localized hyperthermia at 41.5 ± 0.1 °C in rodent models. This tight thermal regulation triggers a genetically encoded thermal bioswitch, enabling precise induction of CAR T-cell transgene expression and cytolytic activity within targeted brain tissue. By establishing metronomic activation protocols, this platform maintains sustained therapeutic efficacy against heterogeneous, antigen negative tumor cells and depletes immunosuppressive myeloid-derived suppressor cells (MDSCs)—providing a noninvasive acoustic framework for site-specific brain tumor immunotherapy.