For example, in a Phase 1 study of an EGFRvIII-specific CAR in GBM, a single dose of the CAR-T cells led to downregulation of the EGFR/EGFRvIII receptor [214], whereas IL13Ra2-specific CAR-T cells co-expressing IL-15 were potent against glioma but led to the rise of tumors with IL13Ra2 downregulation [290]. This evidence concerns the gene IL13RA2 and central nervous system cancer.