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

靶向 CD19 的 CAR-T 细胞可预防 ANCA 诱发的急性肾损伤

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作者:Dörte Lodka, Maria Zschummel, Mario Bunse, Anthony Rousselle, Janis Sonnemann, Ralph Kettritz, Uta E Höpken, Adrian Schreiber

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.

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.

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