CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T cell therapy in rheumatic diseases: a review article.
CAR-T cell therapy in rheumatic diseases: a review article.
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CAR-T 细胞疗法最初为治疗血液系统恶性肿瘤而开发,是一种创新的免疫调节疗法,目前也被视为自身免疫病和风湿性疾病的潜在治疗方法。该方法通过基因工程使T细胞表达嵌合抗原受体(CAR),从而靶向致病免疫细胞相关特定抗原。本综述讨论CAR-T 治疗系统性红斑狼疮(SLE)、类风湿关节炎(RA)和系统性硬化症(SSc)等自身免疫病的可能性。在SLE研究中,CAR-T 可通过靶向疾病过程中的自身反应性B细胞维持缓解,是其重要作用之一。在难治性RA中,CAR-T 也显示出选择性杀伤驱动疾病的免疫细胞的潜在治疗作用。对于SSc,CAR-T 可能代表一种新疗法,因为其可靶向B细胞失调及驱动疾病病理的纤维化过程。新证据提示CAR-T 还可能用于干燥综合征和皮肌炎等疾病。CAR-T 疗法具有精准、持久及可能实现长期缓解的前景,但仍面临细胞因子释放综合征、免疫毒性和治疗可负担性等问题。开发CAR调节性T细胞(CAR-Treg)及先进基因编辑技术有望提高疗法特异性和安全性。
此外,还需开展临床试验及长期研究,以确立这一创新方法的疗效、安全性和经济可行性。本综述强调了CAR-T 疗法管理风湿性疾病、尤其难治性病例的变革潜力。CAR-T 可实现靶向免疫调节,并尽量减少全身免疫抑制,有望重塑治疗模式并改善自身免疫病结局。
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 Sj gren'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.
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