Two teams of researchers working with lead author Dr. Wendell Lim demonstrated the use of synNotch-engineered CD4+ T cells directed towards tissue-specific antigens, triggering the local release of various disease-specific payloads. Reddy et al. utilized this technology to suppress CAR T cell cytotoxicity in on-target/off-tumor tissues and to suppress immune rejection in transplanted organs, while Simic and Watchmaker et al. demonstrated its ability to induce CAR expression only in the brain and to specifically deliver payloads that suppress neuroinflammation.