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首页> 外文期刊>Biotechnology Progress >N-Linked Glycosylation is an Important Parameter for Optimal Selection of Cell Lines Producing Biopharmaceutical Human IgG
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N-Linked Glycosylation is an Important Parameter for Optimal Selection of Cell Lines Producing Biopharmaceutical Human IgG

机译：N-联糖基化是生产生物药物人IgG的细胞系最佳选择的重要参数

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We studied the variations in N-linked glycosylation of human IgG molecules derived from 105 different stable cell lines each expressing one of the six different antibodies.Antibody expression was based on glutamine synthetase selection technology in suspension growing CHO-K1SV cells.The glycans detected on the Fc fragment were mainly of the core-fucosylated complex type containing zero or one galactose and little to no sialic acid.The glycosylation was highly consistent for the same cell line when grown multiple times,indicating the robustness of the production and glycan analysis procedure.However,a twofold to threefold difference was observed in the level of galactosylation and/or non-core-fucosylation between the 105 different cell lines,suggesting clone-to-clone variation.These differences may change the Fc-mediated effector functions by such antibodies.Large variation was also observed in the oligomannose-5 glycan content,which,when present,may lead to undesired rapid clearance of the antibody in vivo.Statistically significant differences were noticed between the various glycan parameters for the six different antibodies,indicating that the variable domains and/or light chain isotype influence Fc glycosylation.The glycosylation altered when batch production in shaker was changed to fed-batch production in bioreactor,but was consistent again when the process was scaled from 400 to 5,000 L.Taken together,the observed clone-to-clone glycosylation variation but batch-to-batch consistency provides a rationale for selection of optimal production cell lines for large-scale manufacturing of biopharmaceutical human IgG.
机译：我们研究了源自105种不同稳定细胞系的人IgG分子的N联糖基化的变化，这些稳定细胞系分别表达六种不同抗体之一。抗体的表达基于谷氨酰胺合成酶选择技术在悬浮生长的CHO-K1SV细胞中的检测。 Fc片段主要是核心-岩藻糖基化的复合物类型，其含有零个或一个半乳糖并且几乎没有唾液酸。多次生长时，同一细胞系的糖基化高度一致，表明生产和聚糖分析程序的鲁棒性。然而，在105种不同的细胞系之间观察到半乳糖基化和/或非核心岩藻糖基化水平存在两到三倍的差异，这表明克隆之间存在变异。这些差异可能会通过此类抗体改变Fc介导的效应子功能还观察到寡甘露糖5聚糖含量存在较大差异，如果存在，可能会导致不期望的快速清除六种不同抗体的各种聚糖参数之间存在统计学上的显着差异，表明可变域和/或轻链同种型会影响Fc糖基化。当摇床中的批量生产更改为补料分批时，糖基化发生了变化。在生物反应器中进行生产，但当该过程从400 L扩展到5,000 L时再次保持一致。总的来说，观察到的克隆到克隆糖基化变化但批间一致性为选择大型生产最佳细胞系提供了依据生物制药人IgG的大规模生产。

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