For instance, combination of a first generation prostate cancer targeting CAR (signal 1) with a TGFBR2:4-1BB CSR (signal 2) and a IL-4/7R CCR (signal 3) has produced promising results in a mouse model of pancreatic cancer, by splitting engineered T cell signals in a TME specific manner [221]. The gene discussed is TGFBR2; the disease is prostate carcinoma.