Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy.

Autor:	Nunez D; Department of Computational Biology, Cabaletta Bio, Philadelphia, PA, USA., Patel D; Department of Protein and Molecular Biology, Cabaletta Bio, Philadelphia, PA, USA., Volkov J; Department of Translational Medicine, Cabaletta Bio, Philadelphia, PA, USA., Wong S; Department of Protein and Molecular Biology, Cabaletta Bio, Philadelphia, PA, USA., Vorndran Z; Department of Translational Medicine, Cabaletta Bio, Philadelphia, PA, USA., Müller F; Department of Medicine 5, Haematology and Oncology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany., Aigner M; Department of Medicine 5, Haematology and Oncology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany., Völkl S; Department of Medicine 5, Haematology and Oncology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany., Mackensen A; Department of Medicine 5, Haematology and Oncology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany., Schett G; Department of Medicine 3, Rheumatology and Immunology, Friedrich Alexander University Erlangen-Nürnberg (FAU) and University Hospital Erlangen, Erlangen, Germany., Basu S; Department of Translational Medicine, Cabaletta Bio, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2023 Sep 01; Vol. 31, pp. 101104. Date of Electronic Publication: 2023 Sep 01 (Print Publication: 2023).
DOI:	10.1016/j.omtm.2023.08.023
Abstrakt:	Chimeric antigen receptor (CAR) T cells targeting CD19 + B cells have demonstrated efficacy in refractory systemic lupus erythematosus (SLE). Although initial clinical data suggest that anti-CD19 CAR T cell therapy is well tolerated and highly effective, the immunologic consequences of CAR T cell therapy in SLE patients remain unclear. We profiled serum in six refractory SLE patients prior to and 3 months following CAR T cell infusion. Three months post T cell infusion, the inflammatory cytokines IL-6 and TNFα decreased in patient sera. This was accompanied by elevations in serum IL-7 and BAFF. Furthermore, SLE-associated antibodies dropped profoundly in five of six patients. Last, consistent with other reports of CD19 CAR T therapy in B cell malignancies, we were able to show marginal impact of anti-CD19 CART therapy on pre-existing humoral immune responses in SLE patients. Together, these results provide insights into the mechanisms of efficacy of anti-CD19 CAR T cell therapy in SLE. Competing Interests: D.N., D.P., J.V., S.W., Z.V., and S.B. are employees of Cabaletta Bio. G.S. has received speaker honoraria and consulting fees from BMS, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. A.M. has received speaker honoraria and consulting fees from BMS/Celgene, Miltenyi Biomedicine, BioNTech, KITE/Gilead, and Novartis. (© 2023 The Author(s).)
Databáze:	MEDLINE
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