去免疫生物治疗药物的设计与工程
Design and engineering of deimmunized biotherapeutics.
作者信息
Griswold Karl E, Bailey-Kellogg Chris
机构信息
Thayer School of Engineering, Dartmouth, Hanover, NH, United States; Stealth Biologics LLC, Lyme, NH, United States.
Stealth Biologics LLC, Lyme, NH, United States; Department of Computer Science, Dartmouth, Hanover, NH, United States.
出版信息
Curr Opin Struct Biol. 2016 Aug;39:79-88. doi: 10.1016/j.sbi.2016.06.003. Epub 2016 Jun 17.
Abstract
Therapeutic proteins are powerful next-generation drugs able to effectively treat diverse and devastating diseases, but the development and use of biotherapeutics entails unique challenges and risks. In particular, protein drugs are subject to immune surveillance in the human body, and ensuing antidrug immune responses can cause a wide range of problems including altered pharmacokinetics, loss of efficacy, and even life-threating complications. Here we review recent progress in technologies for engineering deimmunized biotherapeutics, placing particular emphasis on deletion of immunogenic antibody and T cell epitopes via experimentally or computationally guided mutagenesis.
摘要
治疗性蛋白质是强大的下一代药物，能够有效治疗各种严重疾病，但生物治疗药物的开发和使用带来了独特的挑战和风险。特别是，蛋白质药物在人体内会受到免疫监视，随之产生的抗药物免疫反应会引发一系列问题，包括药代动力学改变、疗效丧失，甚至危及生命的并发症。在这里，我们综述了工程化去免疫生物治疗药物技术的最新进展，特别强调通过实验或计算指导的诱变删除免疫原性抗体和T细胞表位。
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