Wobma Holly, Chang Joyce C, Prockop Susan E
Division of Immunology.
Division of Hematology-Oncology, Boston Children's Hospital, Boston, Massachusetts, USA.
Curr Opin Rheumatol. 2025 Mar 1;37(2):128-135. doi: 10.1097/BOR.0000000000001062. Epub 2024 Nov 1.
PURPOSE OF REVIEW: This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells. RECENT FINDINGS: To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response. SUMMARY: Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.
综述目的:本综述提供了自身免疫性疾病工程细胞疗法这一快速发展领域的最新进展,主要聚焦于嵌合抗原受体(CAR)T细胞的临床经验及相关研究。 最新发现:迄今为止,两个描述CAR T细胞疗法治疗系统性红斑狼疮(SLE)的病例系列表明,先前治疗难治性疾病的患者可实现无药缓解。尽管使用了不同的CAR构建体和淋巴细胞清除方案,但这些研究的结果相似。虽然尚不清楚所描述的患者是否真的已治愈,但大多数缓解在治疗后1至2年的最后随访时仍持续存在。与此同时,机制研究正在揭示短暂性B细胞清除如何介导持久益处。鉴于SLE中令人鼓舞的数据,CAR T细胞和其他新型B细胞清除剂(如双特异性T细胞衔接器)目前正在被评估用于治疗其他自身免疫性疾病,目标是实现持久反应。 总结:近期报告强调细胞疗法是治疗难治性自身免疫性疾病患者的一种有前景的策略;然而,经验仍然有限,预计对这种治疗方法的更深入了解将迅速出现。
Curr Opin Rheumatol. 2025-3-1
Rheumatology (Oxford). 2024-5-2
Beijing Da Xue Xue Bao Yi Xue Ban. 2024-12-18
Front Immunol. 2024-12-19
Int J Mol Sci. 2024-9-29
Ugeskr Laeger. 2024-11-18
Chin Med J (Engl). 2024-5-20
Joint Bone Spine. 2024-9
Front Immunol. 2025-7-18
Nat Rev Rheumatol. 2025-7-2
Mol Biol Rep. 2025-2-20