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嵌合抗原受体T细胞疗法在自身免疫性疾病中的应用

Chimeric antigen receptor T-cell therapy in autoimmune diseases.

作者信息

Liu Jie, Zhao Yan, Zhao Hai

机构信息

Department of Neurosurgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Department of Respiratory, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

出版信息

Front Immunol. 2024 Nov 19;15:1492552. doi: 10.3389/fimmu.2024.1492552. eCollection 2024.

Abstract

The administration of T cells that have been modified to carry chimeric antigen receptors (CARs) aimed at B cells has been an effective strategy in treating B cell malignancies. This breakthrough has spurred the creation of CAR T cells intended to specifically reduce or alter the faulty immune responses associated with autoimmune disorders. Early positive outcomes from clinical trials involving CAR T cells that target the B cell protein CD19 in patients suffering from autoimmune diseases driven by B cells have been reported. Additional strategies are being developed to broaden the use of CAR T cell therapy and enhance its safety in autoimmune conditions. These include employing chimeric autoantireceptors (CAAR) to specifically eliminate B cells that are reactive to autoantigens, and using regulatory T cells (Tregs) engineered to carry antigen-specific CARs for precise immune modulation. This discussion emphasizes key factors such as choosing the right target cell groups, designing CAR constructs, defining tolerable side effects, and achieving a lasting immune modification, all of which are critical for safely integrating CAR T cell therapy in treating autoimmune diseases.

摘要

给予经过改造以携带针对B细胞的嵌合抗原受体(CAR)的T细胞,已成为治疗B细胞恶性肿瘤的有效策略。这一突破促使人们创建了旨在特异性减少或改变与自身免疫性疾病相关的错误免疫反应的CAR-T细胞。据报道,在涉及针对由B细胞驱动的自身免疫性疾病患者的B细胞蛋白CD19的CAR-T细胞的临床试验中,早期取得了积极成果。正在开发其他策略以扩大CAR-T细胞疗法的应用范围并提高其在自身免疫性疾病中的安全性。这些策略包括使用嵌合自身抗原受体(CAAR)特异性清除对自身抗原有反应的B细胞,以及使用经过工程改造以携带抗原特异性CAR的调节性T细胞(Treg)进行精确的免疫调节。本讨论强调了选择合适的靶细胞群体、设计CAR构建体、确定可耐受的副作用以及实现持久的免疫修饰等关键因素,所有这些对于将CAR-T细胞疗法安全地整合到自身免疫性疾病的治疗中至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/54d9/11611814/e212e96adc94/fimmu-15-1492552-g001.jpg

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