Anti-CD19 CAR T cell therapy induces CNS-specific immune alterations in multiple sclerosis

Although current immunotherapies control relapses, they have limited impact on progression, likely due to poor CNS penetration and failure to target meningeal B cell follicles and activated myeloid cells. Chimeric antigen receptor (CAR) T cells can infiltrate tissues, but their ability to access and eliminate CNS-resident immune cells has remained unclear.

We treated five individuals with progressive or relapsing-remitting MS with anti-CD19 CAR T cells to assess safety, CNS bioavailability, and compartment-specific effects. Treatment was well tolerated and induced profound remodeling of the CNS B cell pool, with sustained reduction of cerebrospinal fluid humoral biomarkers. CNS-infiltrating CAR T cells selectively upregulated PDE7B, suggesting a CNS-specific biomarker and trafficking mediator.