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<p>CAR-T cells (CAR-Ts) are genetically engineered T lymphocytes to express a receptor construct bearing an extracellular recognition domain that guides the killing specificity, a transmembrane domain, and an intracellular domain that elicits effector signaling. Upon encountering the target cell, CAR-Ts accomplish their cytolytic effector function directly via engagement of pro-apoptotic pathways and exocytosis of perforin and granzymes, or indirectly via secretion of cytokines that activate NK cells. Autologous CAR-Ts, bearing an extracellular recognition domain specific for the B-cell surface markers CD19 or BCMA, were initially approved for the treatment of late-stage hematologic malignancies. The last five years, mounting evidence from small studies in humans, employing autologous CAR-Ts targeting CD19 to selectively eliminate CD19 + cell subsets from the pool of the B-cell lineage, have revealed acceptable safety profile and encouraging efficacy in treatment-resistant systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Herein, we focus on a series of groundbreaking reports published within 2025 that enlighten the arising transformational potential and the emerging challenges of the CAR-based therapies regarding the management of life-threatening endotypes of autoimmune diseases.</p>

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Chimeric antigen receptor (CAR) therapies for precise eradication of pathogenic cells in autoimmunity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月6日

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  • George D. Kalliolias,
  • Efthimia K. Basdra,
  • Athanasios G. Papavassiliou

摘要

CAR-T cells (CAR-Ts) are genetically engineered T lymphocytes to express a receptor construct bearing an extracellular recognition domain that guides the killing specificity, a transmembrane domain, and an intracellular domain that elicits effector signaling. Upon encountering the target cell, CAR-Ts accomplish their cytolytic effector function directly via engagement of pro-apoptotic pathways and exocytosis of perforin and granzymes, or indirectly via secretion of cytokines that activate NK cells. Autologous CAR-Ts, bearing an extracellular recognition domain specific for the B-cell surface markers CD19 or BCMA, were initially approved for the treatment of late-stage hematologic malignancies. The last five years, mounting evidence from small studies in humans, employing autologous CAR-Ts targeting CD19 to selectively eliminate CD19 + cell subsets from the pool of the B-cell lineage, have revealed acceptable safety profile and encouraging efficacy in treatment-resistant systemic lupus erythematosus, systemic sclerosis, and idiopathic inflammatory myositis. Herein, we focus on a series of groundbreaking reports published within 2025 that enlighten the arising transformational potential and the emerging challenges of the CAR-based therapies regarding the management of life-threatening endotypes of autoimmune diseases.