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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 |
| ISSN: | 0003-4967 |
| Publisher: | BMJ Publishing Group |
| Volume: | 83 |
| Number: | 4 |
| 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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