Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, Baltimore, MD, United States.
Pharmacology/Toxicology Branch I, Division of Clinical Evaluation and Pharmacology/Toxicology, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD, United States.
Front Immunol. 2018 Nov 2;9:2485. doi: 10.3389/fimmu.2018.02485. eCollection 2018.
Immunotherapy is revolutionizing health care, with the majority of high impact "drugs" approved in the past decade falling into this category of therapy. Despite considerable success, glycosylation-a key design parameter that ensures safety, optimizes biological response, and influences the pharmacokinetic properties of an immunotherapeutic-has slowed the development of this class of drugs in the past and remains challenging at present. This article describes how optimizing glycosylation through a variety of glycoengineering strategies provides enticing opportunities to not only avoid past pitfalls, but also to substantially improve immunotherapies including antibodies and recombinant proteins, and cell-based therapies. We cover design principles important for early stage pre-clinical development and also discuss how various glycoengineering strategies can augment the biomanufacturing process to ensure the overall effectiveness of immunotherapeutics.
免疫疗法正在彻底改变医疗保健行业,过去十年中批准的大多数具有重大影响的“药物”都属于这一治疗类别。尽管取得了相当大的成功,但糖基化(确保安全性、优化生物反应并影响免疫疗法药代动力学特性的关键设计参数)在过去减缓了这类药物的发展,目前仍然具有挑战性。本文描述了通过各种糖基工程策略优化糖基化如何为避免过去的陷阱提供诱人的机会,同时还能大大改善免疫疗法,包括抗体和重组蛋白以及基于细胞的疗法。我们介绍了在早期临床前开发阶段非常重要的设计原则,还讨论了各种糖基工程策略如何增强生物制造过程,以确保免疫疗法的整体效果。