PDF(Pubmed)
Abstract：
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient\'s refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus.
摘要：
系统性红斑狼疮（SLE）是一种慢性自身免疫性疾病，可以影响多个器官系统，并且在其表现和对治疗的反应方面具有异质性。当被诊断为童年时，与成人SLE相比，SLE的发病率和死亡率增加。通常需要大量免疫抑制，有明显副作用的风险。对于患有严重或难治性疾病的患者,仍然存在对能够改善疾病控制并减少糖皮质激素和其他毒性药物暴露的新疗法的显著未满足的需求。SLE的发病机制涉及B细胞失调和自身抗体的产生,这是这种疾病的标志。目前批准的B细胞定向疗法通常导致不完全的B细胞消耗,并且可能不靶向负责SLE自身抗体的长寿命浆细胞。假设通过持续消除B细胞和浆母细胞，CART疗法可以阻止患者自身免疫并防止器官损伤，因为目前的B细胞消耗疗法难以治疗。在此，我们总结了目前利用CART细胞治疗SLE的临床前和临床数据，并讨论了这种治疗狼疮的未来。
