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