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@ARTICLE{Reincke:265939,
author = {Reincke, Momsen and von-Wardenburg, Niels-Oliver and
Homeyer, Marie Alice and Kornau, Hans-Christian and Spagni,
Gregorio and Li, Lucie Y and Kreye, Jakob and
Sánchez-Sendín, Elisa and Blumenau, Sonja and Stappert,
Dominik and Radbruch, Helena and Hauser, Anja E and
Künkele, Annette and Edes, Inan and Schmitz, Dietmar and
Prüss, Harald},
title = {{C}himeric autoantibody receptor {T} cells deplete {NMDA}
receptor-specific {B} cells.},
journal = {Cell},
volume = {186},
number = {23},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {DZNE-2023-01062},
pages = {5084 - 5097.e18},
year = {2023},
abstract = {Anti-NMDA receptor (NMDAR) autoantibodies cause NMDAR
encephalitis, the most common autoimmune encephalitis,
leading to psychosis, seizures, and autonomic dysfunction.
Current treatments comprise broad immunosuppression or
non-selective antibody removal. We developed NMDAR-specific
chimeric autoantibody receptor (NMDAR-CAAR) T cells to
selectively eliminate anti-NMDAR B cells and disease-causing
autoantibodies. NMDAR-CAARs consist of an extracellular
multi-subunit NMDAR autoantigen fused to intracellular
4-1BB/CD3ζ domains. NMDAR-CAAR T cells recognize a large
panel of human patient-derived autoantibodies, release
effector molecules, proliferate, and selectively kill
antigen-specific target cell lines even in the presence of
high autoantibody concentrations. In a passive transfer
mouse model, NMDAR-CAAR T cells led to depletion of an
anti-NMDAR B cell line and sustained reduction of
autoantibody levels without notable off-target toxicity.
Treatment of patients may reduce side effects, prevent
relapses, and improve long-term prognosis. Our preclinical
work paves the way for CAAR T cell phase I/II trials in
NMDAR encephalitis and further autoantibody-mediated
diseases.},
keywords = {Animals / Humans / Mice / Autoantibodies: metabolism /
Encephalitis: metabolism / Encephalitis: therapy /
Receptors, N-Methyl-D-Aspartate / T-Lymphocytes / Autoimmune
Diseases / Disease Models, Animal / CAAR T cell (Other) /
CAAR T cell (Other) / CAAR T cell (Other) / CAAR T cell
(Other) / CAAR T cell (Other) / CAAR T cell (Other) / NMDA
receptor encephalitis (Other) / T cells (Other) / autoimmune
encephalitis (Other) / autoimmunity (Other) / cell therapy
(Other) / chimeric autoantibody receptor (Other) /
Autoantibodies (NLM Chemicals) / Receptors,
N-Methyl-D-Aspartate (NLM Chemicals)},
cin = {AG Prüß / LAT / AG Schmitz},
ddc = {610},
cid = {I:(DE-2719)1810003 / I:(DE-2719)1040190 /
I:(DE-2719)1810004},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 351 -
Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
experiment = {EXP:(DE-2719)LAT-20190308},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37918394},
doi = {10.1016/j.cell.2023.10.001},
url = {https://pub.dzne.de/record/265939},
}