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CAR-T 细胞疗法治疗自身免疫性疾病的研究进展。

Frontiers in CAR-T cell therapy for autoimmune diseases.

机构信息

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

出版信息

Trends Pharmacol Sci. 2024 Sep;45(9):839-857. doi: 10.1016/j.tips.2024.07.005. Epub 2024 Aug 14.

Abstract

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has demonstrated significant success in treating cancers. The potential of CAR-T cells is now being explored in the context of autoimmune diseases. Recent clinical trials have shown sustained and profound elimination of autoreactive B cells by CAR-T cells, leading to promising autoimmune disease control with minimal safety concerns. These encouraging results have inspired further investigation into CAR-T cell applications for a broader range of autoimmune diseases and the development of advanced cell products with improved efficacy and safety. In this review, we discuss the mechanisms by which CAR-T cells target autoimmune conditions, summarize current preclinical models, and highlight ongoing clinical trials, including CAR-T therapy design, clinical outcomes, and challenges. Additionally, we discuss the limitations and future directions of CAR-T therapy in the treatment of autoimmune diseases.

摘要

嵌合抗原受体 (CAR)-修饰的 T (CAR-T) 细胞疗法在治疗癌症方面取得了显著成功。CAR-T 细胞的潜力现在正在自身免疫性疾病的背景下进行探索。最近的临床试验表明,CAR-T 细胞可以持续且深度地清除自身反应性 B 细胞,从而在最小的安全性担忧下实现有希望的自身免疫性疾病控制。这些令人鼓舞的结果激发了对 CAR-T 细胞在更广泛的自身免疫性疾病中的应用以及具有更高疗效和安全性的先进细胞产品的进一步研究。在这篇综述中,我们讨论了 CAR-T 细胞靶向自身免疫性疾病的机制,总结了当前的临床前模型,并强调了正在进行的临床试验,包括 CAR-T 治疗设计、临床结果和挑战。此外,我们还讨论了 CAR-T 疗法在治疗自身免疫性疾病方面的局限性和未来方向。

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