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CD19嵌合抗原受体T细胞疗法:自身免疫性风湿性疾病的新曙光?

CD19 CAR-T cell therapy: a new dawn for autoimmune rheumatic diseases?

作者信息

Rangel-Peláez Carlos, Martínez-Gutiérrez Laura, Tristán-Manzano María, Callejas José Luis, Ortego-Centeno Norberto, Martín Francisco, Martín Javier

机构信息

Institute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.

LentiStem Biotech, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Granada, Spain.

出版信息

Front Immunol. 2024 Dec 17;15:1502712. doi: 10.3389/fimmu.2024.1502712. eCollection 2024.

Abstract

Autoimmune rheumatic diseases (ARDs), such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, involve dysregulated immune responses causing chronic inflammation and tissue damage. Despite advancements in clinical management, many patients do not respond to current treatments, which often show limited efficacy due to the persistence of autoreactive B cells. Chimeric antigen receptor (CAR)-T cell therapy, which has shown success in oncology for B cell malignancies, targets specific antigens and involves the adoptive transfer of genetically engineered T cells. CD19 CAR-T cells, in particular, have shown promise in depleting circulating B cells and achieving clinical remission. This review discusses the potential of CD19 CAR-T cells in ARDs, highlighting clinical achievements and addressing key considerations such as optimal target cell populations, CAR construct design, acceptable toxicities, and the potential for lasting immune reset, crucial for the safe and effective adoption of CAR-T cell therapy in autoimmune treatments.

摘要

自身免疫性风湿性疾病(ARDs),如类风湿性关节炎、系统性红斑狼疮和系统性硬化症,涉及免疫反应失调,导致慢性炎症和组织损伤。尽管临床管理取得了进展,但许多患者对目前的治疗没有反应,由于自身反应性B细胞的持续存在,这些治疗往往疗效有限。嵌合抗原受体(CAR)-T细胞疗法在治疗B细胞恶性肿瘤的肿瘤学领域已取得成功,该疗法靶向特定抗原,并涉及过继转移基因工程改造的T细胞。特别是CD19 CAR-T细胞,在消耗循环B细胞和实现临床缓解方面已显示出前景。本综述讨论了CD19 CAR-T细胞在ARDs中的潜力,强调了临床成果,并探讨了一些关键因素,如最佳靶细胞群体、CAR构建体设计、可接受的毒性以及持久免疫重置的可能性,这些对于在自身免疫治疗中安全有效地采用CAR-T细胞疗法至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/819e/11685126/1141d3c325d2/fimmu-15-1502712-g001.jpg

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