Jiskoot Wim, Kijanka Grzegorz, Randolph Theodore W, Carpenter John F, Koulov Atanas V, Mahler Hanns-Christian, Joubert Marisa K, Jawa Vibha, Narhi Linda O
Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, RA Leiden 2300, The Netherlands.
Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado - Boulder, Boulder, Colorado 80309.
J Pharm Sci. 2016 May;105(5):1567-1575. doi: 10.1016/j.xphs.2016.02.031. Epub 2016 Apr 1.
The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.
临床治疗性蛋白质和商业治疗性蛋白质的成功率正在迅速提高，但其潜在的免疫原性一直令人担忧。在过去几年中，为研究各种产品相关属性（特别是几种类型的聚集体和颗粒）和治疗方案（如剂量、给药时间表和给药途径）在引发不良免疫反应中的重要性而开展的大多数研究都使用了多种小鼠模型中的一种。在这篇综述中，我们讨论了为此目的而使用的不同小鼠模型的实用性和缺点。此外，我们总结了这些模型给我们带来的经验教训以及它们所带来的一些挑战。最后，我们为未来利用小鼠模型进行研究提供建议，以增进我们对可能导致蛋白质免疫原性的关键因素的理解。
