PT - JOURNAL ARTICLE AU - Sasha Gupta AU - Milos Simic AU - Sharon A. Sagan AU - Chanelle Shepherd AU - Jason Duecker AU - Raymond A. Sobel AU - Ravi Dandekar AU - Gregory F. Wu AU - Wesley Wu AU - John E. Pak AU - Stephen L. Hauser AU - Wendell Lim AU - Michael R. Wilson AU - Scott S. Zamvil TI - CAR-T Cell–Mediated B-Cell Depletion in Central Nervous System Autoimmunity AID - 10.1212/NXI.0000000000200080 DP - 2023 Mar 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e200080 VI - 10 IP - 2 4099 - http://nn.neurology.org/content/10/2/e200080.short 4100 - http://nn.neurology.org/content/10/2/e200080.full SO - Neurol Neuroimmunol Neuroinflamm2023 Mar 01; 10 AB - Background and Objectives Anti-CD20 monoclonal antibody (mAb) B-cell depletion is a remarkably successful multiple sclerosis (MS) treatment. Chimeric antigen receptor (CAR)-T cells, which target antigens in a non-major histocompatibility complex (MHC)–restricted manner, can penetrate tissues more thoroughly than mAbs. However, a previous study indicated that anti-CD19 CAR-T cells can paradoxically exacerbate experimental autoimmune encephalomyelitis (EAE) disease. We tested anti-CD19 CAR-T cells in a B-cell–dependent EAE model that is responsive to anti-CD20 B-cell depletion similar to the clinical benefit of anti-CD20 mAb treatment in MS.Methods Anti-CD19 CAR-T cells or control cells that overexpressed green fluorescent protein were transferred into C57BL/6 mice pretreated with cyclophosphamide (Cy). Mice were immunized with recombinant human (rh) myelin oligodendrocyte protein (MOG), which causes EAE in a B-cell–dependent manner. Mice were evaluated for B-cell depletion, clinical and histologic signs of EAE, and immune modulation.Results Clinical scores and lymphocyte infiltration were reduced in mice treated with either anti-CD19 CAR-T cells with Cy or control cells with Cy, but not with Cy alone. B-cell depletion was observed in peripheral lymphoid tissue and in the CNS of mice treated with anti-CD19 CAR-T cells with Cy pretreatment. Th1 or Th17 populations did not differ in anti-CD19 CAR-T cell, control cell-treated animals, or Cy alone.Discussion In contrast to previous data showing that anti-CD19 CAR-T cell treatment exacerbated EAE, we observed that anti-CD19 CAR-T cells ameliorated EAE. In addition, anti-CD19 CAR-T cells thoroughly depleted B cells in peripheral tissues and in the CNS. However, the clinical benefit occurred independently of antigen specificity or B-cell depletion.BM=bone marrow; CAR=chimeric antigen receptor; Cy=cyclophosphamide; DEG=differentially expressed gene; EAE=experimental autoimmune encephalomyelitis; GFP=green fluorescent protein; IP=intraperitoneal; mAb=monoclonal antibody; MHC=major histocompatibility complex; MOG=myelin oligodendrocyte protein; MSVG=mouse stem cell virus–based splice-gag vector; UCSF=University of California, San Francisco