Article
NK cell recovery after CD19.CAR-T cell therapy in systemic sclerosis with pulmonary fibrosis: A case study
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Authors
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Maren Claus
- Leibniz Research Center for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund
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Merle Freitag
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg
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Lea Rodon
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg
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Franca Deicher
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg
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Carsten Watzl
- Leibniz Research Center for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund
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Hanns-Martin Lorenz
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg
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Michael Schmitt
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg
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Wolfgang Merkt
- Department of Hematology, Oncology and Rheumatology, Internal Medicine V, University Hospital Heidelberg, Heidelberg; Department of Rheumatology, University Hospital Düsseldorf, Düsseldorf
| Published: | September 18, 2024 |
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Outline
Text
Introduction: Standard therapy of Systemic Sclerosis (SSc)-associated interstitial lung disease (ILD) can not cure, but only decelerate disease progression. CD19-targeting CAR-T cells have the potential to revolutionize anti-rheumatic therapies by eliminating autoantibodies, yet their effects on downstream Fc-receptor bearing cells such as NK cells is unknown [1], [2].
Methods: As published earlier, we recently treated an Scl70+SSc patient with rapidly progressing ILD (NSIP pattern) for the first time with 3rd generation CD19.CAR-T cells [1], [2]. Within 6 months, lung function improved substantially and pulmonary fibrosis regressed. Here, we show longitudinal data of deep immunophenotyping by 29-color spectral flow cytometry as well as results from ex vivo experiments addressing the role of Scl70-containing immune complexes on the activation of Fc-receptor bearing cells.
Results: The substantial clinical improvement was paralleled by dynamic changes in the NK cell compartment. Longitudinal analysis of peripheral blood mononuclear cells over 18 months revealed that NK cells became a more juvenile, less activated, and less differentiated phenotype during the resolution of fibrosis. Decreasing autoantibodies and decreasing potency to form Scl70-containing immune complexes during prolongued B cell depletion may contribute to this NK cell recovery, suggesting pathogenicity of Scl70 autoantibodies in SSc.
Conclusion: While it warrants further study for confirmation, this report is the first to describe the recovery of FcγR-expressing NK cells by CD19.CAR-T cell-containing immunosuppressive therapy in a systemic autoimmune disease.
References
- 1.
- Merkt W, Freitag M, Claus M, Kolb P, Falcone V, Röhrich M, Rodon L, Deicher F, Andreeva I, Tretter T, Tykocinski LO, Blank N, Watzl C, Schmitt A, Sauer T, Müller-Tidow C, Polke M, Heußel CP, Dreger P, Lorenz HM, Schmitt M. Third-generation CD19.CAR-T cell-containing combination therapy in Scl70+ systemic sclerosis. Ann Rheum Dis. 2024 Mar 12;83(4):543-6. DOI: 10.1136/ard-2023-225174
- 2.
- Kvacskay P, Merkt W. CD19.CAR-T cells versus Obinutuzumab-Who will win the race on deep B cell depletion in systemic autoimmunity? Rheumatology (Oxford). 2024 Mar 9:keae144. DOI: 10.1093/rheumatology/keae144
