Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells

Aleix Rius Rigau1,2, Meilin Xu3,4, Ziyuan Liu1,2

  • 1Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.

Insights

CD19-CAR T cell therapy shows promise for treating systemic sclerosis (SSc). This innovative treatment led to skin tissue regeneration and improved fibrotic disease markers in patients.

Area of Science:

  • Immunology
  • Dermatology
  • Regenerative Medicine

Background:

  • Systemic sclerosis (SSc) is an autoimmune disease causing problematic fibrotic tissue remodeling.
  • Current therapies struggle to reverse SSc-induced fibrosis, necessitating novel regenerative strategies.

Purpose of the Study:

  • To investigate the potential of CD19-CAR T cell therapy to induce tissue regeneration in patients with SSc.
  • To analyze the effects of B cell depletion on skin structure, fibroblast populations, and vascular/epidermal function in SSc.

Main Methods:

  • Analysis of skin biopsy samples from SSc patients treated with CD19-CAR T cell therapy (CASTLE study/named patient use).
  • Histological examination for structural regeneration (e.g., skin papillae).
  • Cyclic in situ hybridization and imaging mass cytometry to assess fibroblast, vascular, and epidermal cell changes.

Main Results:

  • Demonstrated structural regeneration of SSc skin, including recovery of skin papillae.
  • Observed a shift in fibroblast populations towards a physiological state (composition and function).
  • Identified signs of vascular repair and altered epidermal cell function post-therapy.

Conclusions:

  • CD19-CAR T cell therapy may induce significant skin tissue remodeling in SSc.
  • B cell depletion via CD19-CAR T cell therapy shows potential for promoting tissue regeneration in fibrotic diseases like SSc.

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