CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
Annals of the rheumatic diseases - 83(2024), 4 vom: 12. März, Seite 499-507 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lodka, Dörte [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Antineutrophil Cytoplasmic |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 24.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1136/ard-2023-224875 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366730215 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Autoantibodies | |
| 650 | 4 | |a Autoimmune Diseases | |
| 650 | 4 | |a Granulomatosis with polyangiitis | |
| 650 | 4 | |a T-Lymphocyte subsets | |
| 650 | 4 | |a Vasculitis | |
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| 700 | 1 | |a Zschummel, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Bunse, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Rousselle, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Sonnemann, Janis |e verfasserin |4 aut | |
| 700 | 1 | |a Kettritz, Ralph |e verfasserin |4 aut | |
| 700 | 1 | |a Höpken, Uta E |e verfasserin |4 aut | |
| 700 | 1 | |a Schreiber, Adrian |e verfasserin |4 aut | |
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