Alan R Abraham, Panayiotis Maghsoudlou, David A Copland, Lindsay B Nicholson, Andrew D Dick
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引用次数: 0
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.
眼科自身免疫和自身炎症会导致严重的视觉疾病，需要复杂的医疗手段，而且副作用大、缺乏特异性。调节性 T 细胞（Tregs）在免疫平衡和解决免疫反应中发挥着关键作用。多克隆 Treg疗法在治疗自身免疫性疾病方面已显示出疗效。通过基因工程方法产生抗原特异性 Treg 疗法有可能增强治疗反应，减少全身副作用。使用嵌合抗原受体修饰 T 细胞（CAR-T）疗法的细胞疗法在治疗血液恶性肿瘤方面取得了巨大成功。通过对Tregs进行特异性修饰，CAR-Treg疗法在自身免疫性疾病的临床前模型中具有显著疗效，目前已进入1-2期临床试验阶段。本综述总结了CAR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。
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