Optimizing CAR-T cell therapy requires multiple antigen-targeting strategies, such as dual- and trivalent CAR constructs directed against EGFRvIII, IL13Rα2, and EphA2, reducing the likelihood of immune escape.496 Advances in switch-controlled CAR-T cell systems, including synthetic Notch circuits, enable selective activation in high-antigen-density environments while minimizing off-target effects.497 Additionally, hypoxia-sensitive CAR-T cells, engineered to adapt to the oxygen-deprived microenvironment of GBM, offer a novel way to increase specificity while reducing systemic toxicity. This evidence concerns the gene IL13RA2 and glioblastoma.