BioAnalytical Sciences Genentech, South San Francisco, California, USA.
Lonza, Drug Product Services, Basel, Switzerland.
AAPS J. 2017 Nov;19(6):1656-1668. doi: 10.1208/s12248-017-0128-y. Epub 2017 Aug 9.
Therapeutic breakthroughs in a number of retinal degenerative diseases have come about through the development of biotherapeutics administered directly into the eye. As a consequence of their use, we have gained more insight into the immune privileged status of the eye and the various considerations that development, manufacturing, and use of these drugs require. It has been observed that therapeutic proteins injected into the vitreous can elicit an immune response resulting in the production of anti-drug antibodies (ADAs) which can have clinical consequences. This review includes discussion of the anatomy, physiology, and specific area of the eye that are targeted for drug administration. The various immunologic mechanisms involved in the immune responses to intraocularly administered protein are discussed. This review entails discussion on chemistry, manufacturing, and control (CMC) and formulation-related issues that may influence the risk of immunogenicity. Based on the available immunogenicity profile of the marketed intraocular drugs and their reported adverse events, the animal models and the translational gap from animals to human are discussed. Thus, the objective of this review article is to assess the factors that influence immunogenicity in relation to intraocular administration and the steps taken for mitigating immunogenicity risks.
通过直接向眼睛给药的生物疗法，许多视网膜退行性疾病已经取得了治疗突破。由于这些药物的使用，我们对眼睛的免疫特权状态以及开发、制造和使用这些药物所需的各种考虑因素有了更深入的了解。人们已经观察到，注射到玻璃体内的治疗性蛋白质会引起免疫反应，导致产生抗药物抗体（ADA），这可能会产生临床后果。本文综述了讨论药物给药的眼部解剖、生理学和特定区域。讨论了涉及眼内给予蛋白质的免疫反应的各种免疫机制。本文综述了可能影响免疫原性风险的化学、制造和控制（CMC）以及制剂相关问题。基于已上市的眼内药物的可用免疫原性概况及其报告的不良事件，讨论了动物模型和从动物到人类的转化差距。因此，本文的目的是评估影响眼内给药免疫原性的因素以及为降低免疫原性风险而采取的措施。
