The EGFRvIII–SynNotch primed EphA2/IL-13Rα2 CAR (E-SYNC) system is selectively activated by EGFRvIII as the GBM-specific signal, leading to the complete eradication of patient-derived xenografts (PDX) with heterogeneous EGFRvIII expression. This evidence concerns the gene EPHA2 and glioblastoma.