CNS Endothelial Cell Activation Emerges as a Driver of CAR T Cell–Associated Neurotoxicity

Summary: Central nervous system (CNS) toxicity associated with chimeric antigen receptor–based therapeutics has emerged as a significant cause of morbidity and mortality, and insights into the pathophysiology of this syndrome have been lacking. A new study provides evidence that cytokine-induced CNS endothelial cell activation leading to disruption of the blood–brain barrier plays an early and critical role in this phenomenon. These insights provide new opportunities for targeted therapeutic interventions to modulate endothelial cell activation. Cancer Discov; 7(12); 1371–3.