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CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury

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Item Type:Article
Title:CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury
Creators Name:Lodka, D. and Zschummel, M. and Bunse, M. and Rousselle, A. and Sonnemann, J. and Kettritz, R. and Höpken, U.E. and Schreiber, A.
Abstract:OBJECTIVES: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are life-threatening systemic autoimmune diseases manifesting in the kidneys as necrotizing crescentic glomerulonephritis (NCGN). ANCA antigens are myeloperoxidase (MPO) or proteinase 3. Current treatments include steroids, cytotoxic drugs and B cell-depleting antibodies. The use of chimeric antigen receptor (CAR) T cells in autoimmune diseases is a promising new therapeutic approach. We tested the hypothesis that CAR T cells targeting CD19 deplete B cells, including MPO-ANCA-producing B cells, thereby protecting from ANCA-induced NCGN. METHODS: We tested this hypothesis in a preclinical MPO-AAV mouse model. NCGN was established by immunisation of MPO(-/-) mice with murine MPO, followed by irradiation and transplantation with haematopoietic cells from wild-type mice alone or together with either CD19-targeting CAR T cells or control CAR T cells. RESULTS: CD19 CAR T cells efficiently migrated to and persisted in bone marrow, spleen, peripheral blood and kidneys for up to 8 weeks. CD19 CAR T cells, but not control CAR T cells, depleted B cells and plasmablasts, enhanced the MPO-ANCA decline, and most importantly protected from NCGN. CONCLUSION: Our proof-of-principle study may encourage further exploration of CAR T cells as a treatment for ANCA-vasculitis patients with the goal of drug-free remission.
Keywords:Acute Kidney Injury, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antineutrophil Cytoplasmic Antibodies, Glomerulonephritis, Peroxidase, T-Lymphocytes, Animals, Mice
Source:Annals of the Rheumatic Diseases
Publisher:BMJ Publishing Group
Page Range:499-507
Date:12 March 2024
Official Publication:https://doi.org/10.1136/ard-2023-224875
PubMed:View item in PubMed

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