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Letter
Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells
  1. Christina Bergmann1,2,
  2. Fabian Müller2,3,
  3. Jörg H W Distler1,2,4,5,
  4. Andrea-Hermina Györfi4,5,
  5. Simon Völkl2,3,
  6. Michael Aigner2,3,
  7. Sascha Kretschmann2,3,
  8. Hannah Reimann2,3,
  9. Thomas Harrer1,2,
  10. Nadine Bayerl6,
  11. Sebastian Boeltz1,2,
  12. Andreas Wirsching1,2,
  13. Jule Taubmann1,2,
  14. Wolf Rösler2,3,
  15. Bernd Spriewald2,3,
  16. Jochen Wacker1,2,
  17. Armin Atzinger7,
  18. Michael Uder6,
  19. Torsten Kuwert7,
  20. Andreas Mackensen2,3,
  21. Georg Schett1,2
  1. 1 Department of Internal Medicine 3- Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  2. 2 Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  3. 3 Department of Internal Medicine 5-Haematology and Clinical Oncology, FAU Erlangen-Nurnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  4. 4 Department of Rheumatology, Universitatsklinikum Dusseldorf, Dusseldorf, Germany
  5. 5 Hiller Research Unit, University of Düsseldorf, Duesseldorf, Germany
  6. 6 Institute of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  7. 7 Institute of Nuclear Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
  1. Correspondence to Professor Georg Schett, Rheumatology, University of Erlangen, Erlangen, Germany; georg.schett{at}uk-erlangen.de

https://doi.org/10.1136/ard-2023-223952

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    Several lines of evidence suggest a role of B cells in severe systemic sclerosis (SSc) pathophysiology: elevated levels of B-cell stimulating factors, disturbed B-cell homeostasis with expansion of naïve and decrease of memory B cells,1 and antifibrotic effects of B-cell depletion in murine fibrosis models. First randomised controlled trials showed promising efficacy of the CD20-targeting antibody rituximab (RTX)2 3; however, therapeutic efficacy of RTX in SSc remains controversial: while one trial demonstrated significant skin improvement,2 RTX slowed forced vital capacity (FVC) decline in another study but with similar effects compared to the cyclophosphamide control arm.3 As in cases of severe lupus erythematosus (SLE), we speculated that CD20+ B-cell depletion may not be sufficient as B-cell precursors, which are particularly expanded in SSc, and plasmablasts, which may be responsible for autoantibody production, are not targeted via CD20 but via CD19. Of note, autologous stem-cell transplantation overcomes these limitations and has shown remarkable treatment efficacy in severe SSc.4 However, transplant-related mortality is high. Hence, a more tolerable treatment with deep and broad CD19+ B-cell depletion may be more effective. Recently, CD19-chimeric antigen receptor (CAR) T cells showed remarkable effects in refractory SLE5 and first evidence of efficacy in a patient with antisynthetase syndrome,6 suggesting the principle feasibility to intercept B cell-driven autoimmune diseases via CD19-CAR T cells.

    Here, we report for the first time the treatment of a patient with severe, treatment refractory SSc with CD19-CAR T cells. A 60-year-old man presented with diffuse cutaneous SSc with first non-Raynaud’s disease manifestation (skin, lung and heart fibrosis) 22 months before baseline and onset of Raynaud’s phenomenon 28 months before baseline. At baseline, the patient presented with diffuse myocardial fibrosis (cardiac MRI), lung fibrosis (high-resolution computed tomography), pulmonary hypertension (class I with combined precapillary and postcapillary …

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