Neurological complications of current and emerging CAR-T cell therapies

Harnessing an individual patient's immune system to enhance anti-tumor responses has been a long-standing goal in oncology. Multiple immune modulating or immune enhancing therapies have been FDA approved or are under development, utilizing varying strategies to engage the patient's own immune system. One such therapy is chimeric antigen receptor T-cell therapy (CAR-T), in which T-cells are genetically engineered to target specific antigens present on tumor cells. Multiple CAR-T products are currently approved for clinical use, with impressive and durable responses seen in hematologic cancers. With their efficacy for treating cancer comes the risk of complications, including a high frequency of neurologic complications. Based on the success seen with cellular therapies in hematologic cancers, these technologies are being tested for both the use in solid malignancies, including central nervous system tumors, and for their application in non-neoplastic conditions such as autoimmune diseases. As new CAR-T therapies are designed and introduced into clinical practice, it will be important to assess their risks of neurologic toxicity and to develop therapies to either prevent or treat these complications. Here, we provide an overview of the acute and potentially long-term neurologic complications encountered with these novel and powerful cellular therapies, focusing on emerging CAR-T technologies, their associated neurotoxicities and potential interventions to limit such neurologic complications.