Fig. 1

a Schematic of the EchoBack-CAR T cell system. Focused ultrasound (FUS)-induced local hyperthermia activates a heat-sensitive promoter to initiate CAR expression, which in turn triggers antigen-dependent T cell signaling. The resulting intracellular signaling enhances promoter activity, forming a positive feedback loop that sustains CAR expression. b Schematic showing the engineering strategy for optimizing the EchoBack-CAR gene circuit. A library of heat-responsive promoters was screened to identify constructs with minimal basal activity and strong inducibility. To enable prolonged CAR expression following transient FUS stimulation, enhancer elements responsive to CAR signaling pathways (such as NFAT and NF-κB) were incorporated, establishing a self-amplifying gene circuit. c Comparison of different optimized CAR-T systems. This figure was created with BioRender.com