Additionally, tumor-selective protease-activated CARs and activation-inducible TRUCKs (for IL-12 production for instance as described above) confine potentially toxic cytokine secretion to the tumor microenvironments, and similarly, promoters such as NR4A2 and RGS16 have been designed to drive CAR or cytokine expression specifically in the tumor microenvironment, ensuring that the transgene is predominantly active only in tumor tissue, thereby enhancing safety and minimizing off-tumor effects (194, 237–240). This evidence concerns the gene NR4A2 and neoplasm.