Abstract:
Ophthalmic autoimmune and autoinflammatory conditions cause significant visual morbidity and require complex medical treatment complicated by significant side effects and lack of specificity. Regulatory T cells (Tregs) have key roles in immune homeostasis and in the resolution of immune responses. Polyclonal Treg therapy has shown efficacy in treating autoimmune disease. Genetic engineering approaches to produce antigen-specific Treg therapy has the potential for enhanced treatment responses and fewer systemic side effects. Cell therapy using chimeric antigen receptor modified T cell (CAR-T) therapy, has had significant success in treating haematological malignancies. By modifying Tregs specifically, a CAR-Treg approach has been efficacious in preclinical models of autoimmune conditions leading to current phase 1-2 clinical trials. This review summarises CAR structure and design, Treg cellular biology, developments in CAR-Treg therapies, and discusses future strategies to apply CAR-Treg therapy in the treatment of ophthalmic conditions.
摘要:
眼科自身免疫和自身炎症导致显著的视觉发病率,并且需要复杂的药物治疗,其复杂的副作用和缺乏特异性。调节性T细胞(Tregs)在免疫稳态和免疫应答的解决中具有关键作用。多克隆Treg疗法已显示出治疗自身免疫性疾病的功效。产生抗原特异性Treg治疗的基因工程方法具有增强的治疗反应和更少的全身副作用的潜力。使用嵌合抗原受体修饰的T细胞(CAR-T)治疗的细胞治疗,在治疗血液恶性肿瘤方面取得了显著成功。通过特别修改Tregs,CAR-Treg方法在自身免疫疾病的临床前模型中有效,导致目前的1-2期临床试验.这篇综述总结了汽车的结构和设计,Treg细胞生物学,CAR-Treg疗法的发展,并讨论了将CAR-Treg疗法应用于眼科疾病治疗的未来策略。