AAV8 可在灵长类动物眼中诱导先天和适应性免疫反应。
AAV8 Can Induce Innate and Adaptive Immune Response in the Primate Eye.
机构信息
University Eye Hospital, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany; Institute for Ophthalmic Research, Centre for Ophthalmology, University Hospital Tübingen, Tübingen, Germany.
Immunopathology Laboratory, Department of Internal Medicine II, University Hospital Tübingen, Tübingen, Germany.
出版信息
Mol Ther. 2017 Dec 6;25(12):2648-2660. doi: 10.1016/j.ymthe.2017.08.018. Epub 2017 Aug 31.
Abstract
Ocular gene therapy has evolved rapidly into the clinical realm due to promising pre-clinical proof-of-concept studies, recognition of the high unmet medical need of blinding disorders, and the excellent safety profile of the most commonly used vector system, the adeno-associated virus (AAV). With several trials exposing subjects to AAV, investigators independently report about cases with clinically evident inflammation in treated eyes despite the concept of ocular immune privilege. Here, we provide a detailed analysis of innate and adaptive immune response to clinical-grade AAV8 in non-human primates and compare this to preliminary clinical data from a retinal gene therapy trial for CNGA3-based achromatopsia (ClinicalTrials.gov: 02610582).
摘要
由于有前途的临床前概念验证研究、对致盲疾病未满足的高医疗需求的认识，以及最常用的载体系统腺相关病毒 (AAV) 的出色安全性，眼基因治疗已迅速发展到临床领域。随着多项临床试验将受试者暴露于 AAV，研究人员独立报告了在治疗眼中出现明显临床炎症的病例，尽管存在眼部免疫特权的概念。在这里，我们对非人类灵长类动物中临床级 AAV8 的先天和适应性免疫反应进行了详细分析，并将其与基于 CNGA3 的色盲性视锥细胞营养不良的视网膜基因治疗试验的初步临床数据进行了比较（ClinicalTrials.gov：02610582）。
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