Ultrasound priming gated by solid tumor hallmarks to guide CAR-T therapy - PubMed
4 hours ago
- #Solid Tumors
- #CAR-T Therapy
- #Ultrasound Priming
- CAR-T therapy is effective in hematologic cancers but faces challenges in solid tumors.
- Researchers developed SHIFTERS, an AND-gated circuit that converts tumor hallmarks into CD19 under focused ultrasound control.
- SHIFTERS uses split Gal4-VP64 driven by hypoxia and heat-shock promoters, restricting CD19 to sonicated, hallmark-positive areas.
- This enables local CD19 expression to activate synNotch CAR-T cells, achieving strong tumor suppression in 3D and in vivo models.
- SHIFTERS is modular and adaptable to tumor-specific promoters like enAFP for hepatocellular carcinoma, enhancing precision.
- The platform provides a tumor-constrained, ultrasound-controllable system to improve CAR-T therapy precision and efficacy for solid tumors.