Provide education on chimeric antigen receptor (CAR) T-cell therapy in neurological disorders.

The use of autologous CAR T-cells has revolutionized hematologic malignancy outcomes, providing potential cures for previously relapsed and refractory B-cell lymphomas and multiple myeloma. T cells expressing CARs can target specific surface antigens without the need for antigen-presenting cells, short-circuiting T-cell activation and proliferation while potentially having greater tissue penetrance than monoclonal antibodies such as rituximab and ocrelizumab. CAR-Ts are under investigation for the treatment of neurologic disorders including myasthenia gravis, multiple sclerosis, neuromyelitis optica and neurologic malignancies. As there are major difference in CAR design and method of T-cell engineering, neurologists should get better acquainted with different CAR-Ts currently investigated in neurology.

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CAR protein delivery to the cell can be permanent, using integrating viral vectors, or transient, using mRNA. Engineering with integrating vectors requires lymphodepletion chemotherapy and inpatient administration of a single dose by a multidisciplinary team. It is also associated with development of cytokine release syndrome, neurotoxicity and secondary malignancies, limiting its use to refractory or severe diseases. Alternatively, using mRNA  for transient CAR expression relies on repeated intravenous infusions but does not require lymphodepletion, can be safely administered in an outpatient setting, and thus far has not been associated with the common and severe CAR-T toxicities. Both approaches require leukapheresis and some time for manufacturing but have been associated with deep and durable responses.

CAR T-cell therapy represents a burgeoning field  of therapeutic development for neurological disorders. There are specific and potential severe associated toxicities. The implementation and success of CAR T-cell therapy necessitates broad interdisciplinary and multi-institutional collaborations.