Some efforts have focused on the importance of peritumoral vasculature to improve CAR-T therapy penetration in GBM.75,76 p21-activated kinase 4 has been identified as a contributor to endothelial cell dysfunction, specifically in the GBM tumor vascular environment.75 p21-activated kinase 4 inhibition improved T cell infiltration and increased survival in murine models when combined with EGFRvIII-CAR-T therapy. This evidence concerns the gene PAK4 and glioblastoma.