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<p>Systemic sclerosis (SSc) is a complex disease with extensive fibrosis, microvasculopathy, and autoantibodies. Activation of the adaptive immune system involving T cells, B cells, and macrophages along with microvasculopathy is considered early events in disease pathogenesis. Today, immunosuppressives, including anti-B cell biologics, form the foundation of SSc treatment; however, significant therapeutic needs remain unmet. Autologous chimeric antigen receptor (CAR)-T cells, targeting B cell CD19 and inducing deep depletion of B cells, were tested in a few patients with SSc, leading to improvement of skin score, arthritis, digital ulcers, and inflammatory changes in heart and lungs. However, regression of lung fibrosis remains a major therapeutic challenge. In addition, autologous CAR-T cells are a personalized treatment that requires a specialized setting, is not readily available, is costly, and is associated with serious adverse effects, including cytokine release syndrome, neurotoxicity, and increased risk of infection. New developments in CAR T cell technology, including off-the-shelf allogeneic CAR T cells, bispecific CAR-T cells, and CAR NK cells, are being tested in patients with progressive refractory SSc.</p><p><Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p>Key Points</p> <p>• <i>There is unmet therapeutic need for systemic sclerosis(SSc).</i></p> <p>• <i>Autologous CAR-T cells targeting CD19 showed efficacy in SSc, but are a personalized, expensive and not readily available treatment.</i></p> <p>• <i>Off-the-shelf allogeneic CAR-T cells and CAR-NK cells are being evaluated in SSc.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>

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CAR-T cells in systemic sclerosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月4日

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  • Lazaros I. Sakkas,
  • Chistina Katsiari,
  • Vasiliki Syrmou,
  • Ian C. Chikanza

摘要

Systemic sclerosis (SSc) is a complex disease with extensive fibrosis, microvasculopathy, and autoantibodies. Activation of the adaptive immune system involving T cells, B cells, and macrophages along with microvasculopathy is considered early events in disease pathogenesis. Today, immunosuppressives, including anti-B cell biologics, form the foundation of SSc treatment; however, significant therapeutic needs remain unmet. Autologous chimeric antigen receptor (CAR)-T cells, targeting B cell CD19 and inducing deep depletion of B cells, were tested in a few patients with SSc, leading to improvement of skin score, arthritis, digital ulcers, and inflammatory changes in heart and lungs. However, regression of lung fibrosis remains a major therapeutic challenge. In addition, autologous CAR-T cells are a personalized treatment that requires a specialized setting, is not readily available, is costly, and is associated with serious adverse effects, including cytokine release syndrome, neurotoxicity, and increased risk of infection. New developments in CAR T cell technology, including off-the-shelf allogeneic CAR T cells, bispecific CAR-T cells, and CAR NK cells, are being tested in patients with progressive refractory SSc.

Key Points

• There is unmet therapeutic need for systemic sclerosis(SSc).

• Autologous CAR-T cells targeting CD19 showed efficacy in SSc, but are a personalized, expensive and not readily available treatment.

• Off-the-shelf allogeneic CAR-T cells and CAR-NK cells are being evaluated in SSc.