背景:尽管现有治疗方法在管理自身免疫性风湿性疾病(ARD)方面取得了进展,许多患者仍然遇到挑战,如反应不足,难以维持缓解,和副作用。嵌合抗原受体(CAR)T细胞疗法,最初是为癌症开发的,现在已经成为难治性ARD病例的一个有希望的选择。
方法:进行了文献检索,以撰写叙述性综述,探索当前的证据,潜在安全,局限性,潜在的修改,以及CAR-T细胞在ARD中的未来方向。
结果:CAR-T细胞疗法已用于难治性ARDs患者,包括系统性红斑狼疮,抗合成酶综合征,和系统性硬化症,表现出显著的改善。值得注意的反应包括临床症状增强,血清自身抗体滴度降低,和疾病活动的持续缓解。使用动物和人类样品的临床前和体外研究也支持了CAR-T细胞对抗抗中性粒细胞胞质抗体相关血管炎和类风湿性关节炎的功效并阐述了其潜在机制。在谨慎监测不良事件的同时,如细胞因子释放综合征,是至关重要的,该疗法似乎具有很高的耐受性。然而,挑战依然存在,包括成本,由于潜在的CAR-T细胞耗尽,和制造复杂性,敦促开发创新解决方案,以进一步增强ARD中CAR-T细胞疗法的可及性。
结论:CAR-T细胞疗法治疗难治性ARDs具有很高的有效性。虽然目前没有重大警告信号的报告,在治疗效果和安全性之间取得平衡对于采用CAR-T细胞疗法治疗ARD至关重要.此外,技术进步具有巨大的潜力,可以增强对患者的治疗效果,从而确保患者更安全、更有效的疾病控制。
BACKGROUND: Despite advancements in managing autoimmune rheumatic diseases (ARDs) with existing treatments, many patients still encounter challenges such as inadequate responses, difficulty in maintaining remission, and side effects. Chimeric Antigen Receptor (CAR) T-cell therapy, originally developed for cancer, has now emerged as a promising option for cases of refractory ARDs.
METHODS: A search of the literature was conducted to compose a narrative review exploring the current evidence, potential safety, limitations, potential modifications, and future directions of CAR-T cells in ARDs.
RESULTS: CAR-T cell therapy has been administered to patients with refractory ARDs, including systemic lupus erythematosus, antisynthetase syndrome, and systemic sclerosis, demonstrating significant improvement. Notable responses include enhanced clinical symptoms, reduced serum autoantibody titers, and sustained remissions in disease activity. Preclinical and in vitro studies using both animal and human samples also support the efficacy and elaborate on potential mechanisms of CAR-T cells against antineutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis. While cautious monitoring of adverse events, such as cytokine release syndrome, is crucial, the therapy appears to be highly tolerable. Nevertheless, challenges persist, including cost, durability due to potential CAR-T cell exhaustion, and manufacturing complexities, urging the development of innovative solutions to further enhance CAR-T cell therapy accessibility in ARDs.
CONCLUSIONS: CAR-T cell therapy for refractory ARDs has demonstrated high effectiveness. While no significant warning signs are currently reported, achieving a balance between therapeutic efficacy and safety is vital in adapting CAR-T cell therapy for ARDs. Moreover, there is significant potential for technological advancements to enhance the delivery of this treatment to patients, thereby ensuring safer and more effective disease control for patients.