Fig. 3

Next-generation CAR T cells with synNotch circuit for targeting immune-suppressive solid tumors. The immunosuppressive (cold) tumor microenvironment around solid tumors blocks CAR T-cell functions. SynNotch circuit–engineered CAR T cells, designed to detect tumor antigens and induce IL-2, can be locally activated with autocrine IL-2 signaling at solid tumor sites. This local activation forms immuno-active (hot) microenvironment to facilitate increased infiltration into solid tumors, which allows successful elimination of solid tumors in a mouse model