The original system was further modified to accommodate the recognition of various tumor antigen combinations such as ROR1/EpCAM or ROR1/B7-H3 in the breast cancer model [114], GD2/B7-H3 in neuroblastoma [115], EGFRvIII SynNotch that induces expression of EohA2/Il13Ra2 tandem CAR for treatment of glioblastoma [116], or ALPPL2 combined with MCAM or HER2 synNotch CAR combinatorial antigen circuits [117]. The gene discussed is ERBB2; the disease is breast cancer.