Shi Helen H, Goudar Chetan T
First Year Medical Student at Case Western Reserve School of Medicine, Process & Product Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California, 91320.
Biotechnol Bioeng. 2014 Oct;111(10):1907-19. doi: 10.1002/bit.25318. Epub 2014 Aug 7.
With the prevalence of therapeutic monoclonal antibodies (mAbs) in the biopharmaceutical industry, the use of mammalian cell culture systems, particularly Chinese hamster ovary (CHO) cells, has become the main method for the production of therapeutics. Despite their similarity to human cells, one major challenge of mammalian cell based biopharmaceutical production is controlling aberrant glycosylation, especially glycans with five to nine mannose residues-high mannose glycoforms. Glycosylation plays a critical role in determining the therapeutic profile of therapeutic glycoproteins; high mannose glycoforms in particular have been shown to have a significant impact on clinical efficacy and pharmacokinetics. Thus, producing glycoform profiles with consistent levels of high mannose is necessary to reduce batch-to-batch therapeutic variability and to meet regulatory standards. Studies have shown that high mannose glycoforms can be modulated through the genetic engineering of cell lines, addition of inhibitors to key enzymes in the glycosylation pathways, and varying cell culture conditions. Focusing on these three types of techniques, this review will examine and critically assess current methods for high mannose glycosylation control and future developments in this area.
随着治疗性单克隆抗体（mAbs）在生物制药行业的普及，哺乳动物细胞培养系统的使用，特别是中国仓鼠卵巢（CHO）细胞，已成为生产治疗药物的主要方法。尽管它们与人类细胞相似，但基于哺乳动物细胞的生物制药生产的一个主要挑战是控制异常糖基化，特别是具有五到九个甘露糖残基的聚糖——高甘露糖糖型。糖基化在确定治疗性糖蛋白的治疗特性方面起着关键作用；特别是高甘露糖糖型已被证明对临床疗效和药代动力学有重大影响。因此，产生具有一致水平高甘露糖的糖型分布对于减少批次间治疗差异和满足监管标准是必要的。研究表明，高甘露糖糖型可以通过细胞系的基因工程、在糖基化途径中添加关键酶的抑制剂以及改变细胞培养条件来调节。围绕这三种技术类型，本综述将研究并批判性地评估当前控制高甘露糖糖基化的方法以及该领域的未来发展。
