Treatment of multiple sclerosis with CD19-targeting CAR-T-cells

Three patients with refractory MS received CD19-targeting chimeric antigen receptor (CAR)-T-cells (UKT-CART19.1) after standard lymphodepletion and were followed-up for 3, 7 and respectively 12 months. All showed neuroinflammation on magnetic resonance imaging (MRI) and/or clinical deterioration prior to treatment. UKT-CART19.1 was well tolerated, stabilized clinical impairment, and reduced intrathecal antibody levels and inflammatory lesions on MRI imaging. Transient B-cell depletion was followed by reconstitution with predominately naïve B-cells. We propose that CD19-targeting CAR-T-cells are safe and effective in refractory MS warranting further exploration in clinical trials. Notably, this report provides first evidence of neuroimaging responses to CAR-T-cell therapy in MS.