风湿性疾病中的嵌合抗原受体T细胞疗法:一篇综述文章。
CAR-T cell therapy in rheumatic diseases: a review article.
作者信息
Patil Harshwardhan, Bharadwaj Rajath K, Dutta Nilanjana, Subramanian Ramaswamy, Prasad Shiva, Mamadapur Mahabaleshwar
机构信息
Department of Pharmacy Practice, JSS College of Pharmacy, Mysuru, India.
JSS Medical College, Mysuru, India.
出版信息
Clin Rheumatol. 2025 Apr 26. doi: 10.1007/s10067-025-07451-7.
CAR-T cell therapy, a pioneering immune-modulating treatment that was initially designed for hematologic malignancies, is now being considered a potential treatment for autoimmune and rheumatic diseases. This method involves genetically engineering T cells to express chimeric antigen receptors (CARs), allowing them to target specific antigens associated with pathogenic immune cells. The review covers the possibility of CAR-T therapy in the treatment of autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc). The therapy's ability to maintain remission by targeting autoreactive B cells in the course of disease has been an important aspect of studies involving SLE. In refractory RA, CAR-T cells also demonstrate a potential therapeutic modality in selectively killing immune cells driving the disease process. For SSc, CAR-T therapy may represent a novel therapeutic approach because it targets the dysregulated activity of B cells as well as the fibrotic processes that drive the disease pathology. Emerging evidence suggests potential applications in conditions such as Sjögren's syndrome and dermatomyositis. While CAR-T therapy promises accuracy, persistence, and the potential for long-term remission, many problems remain, including the risk of cytokine release syndrome, immune toxicity, and treatment affordability. The development of CAR-Tregs and advanced gene-editing techniques may increase the specificity and safety of therapy. In addition, clinical trials and long-term studies should be conducted to establish the efficacy, safety, and economic feasibility of this innovative approach. This review underscores the transformative potential of CAR-T therapy in the management of rheumatic diseases, particularly in refractory cases. Offering targeted immunomodulation with a minimum of systemic immune suppression, CAR-T therapy could redefine therapeutic paradigms and offer hope for improved outcomes in autoimmune diseases.
嵌合抗原受体T细胞(CAR-T)疗法是一种开创性的免疫调节治疗方法,最初设计用于治疗血液系统恶性肿瘤,现在正被视为自身免疫性疾病和风湿性疾病的一种潜在治疗方法。这种方法涉及对T细胞进行基因工程改造,使其表达嵌合抗原受体(CAR),从而使其能够靶向与致病性免疫细胞相关的特定抗原。本文综述了CAR-T疗法在治疗系统性红斑狼疮(SLE)、类风湿关节炎(RA)、系统性硬化症(SSc)等自身免疫性疾病方面的可能性。在SLE的研究中,该疗法通过在疾病过程中靶向自身反应性B细胞来维持缓解的能力一直是一个重要方面。在难治性RA中,CAR-T细胞在选择性杀死驱动疾病进程的免疫细胞方面也显示出潜在的治疗方式。对于SSc,CAR-T疗法可能代表一种新的治疗方法,因为它针对B细胞的失调活性以及驱动疾病病理的纤维化过程。新出现的证据表明,该疗法在干燥综合征和皮肌炎等疾病中也有潜在应用。虽然CAR-T疗法有望实现精准、持久且有长期缓解的潜力,但仍存在许多问题,包括细胞因子释放综合征、免疫毒性和治疗费用可及性等风险。CAR-T调节性T细胞(CAR-Tregs)的开发和先进的基因编辑技术可能会提高治疗的特异性和安全性。此外,还应进行临床试验和长期研究,以确定这种创新方法的疗效、安全性和经济可行性。这篇综述强调了CAR-T疗法在风湿性疾病管理中的变革潜力,特别是在难治性病例中。CAR-T疗法以最小的全身免疫抑制提供靶向免疫调节,可能会重新定义治疗模式,并为改善自身免疫性疾病的治疗结果带来希望。