Optimization of humanized IgGs in glycoengineered Pichia pastoris
Optimization of humanized IgGs in glycoengineered Pichia pastoris
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DOI：
10.1038/nbt1178
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发表时间：
2006-02-01
影响因子：
46.9
通讯作者：
Gerngross, TU
中科院分区：
文献类型：
--
作者：
Li, HJ;Sethuraman, N;Gerngross, TU
作为发展最快的一类治疗性蛋白质，单克隆抗体（mAb）代表了一种主要的潜在药物类别（1）。人抗体在其天然状态下被糖基化，并且所有临床上批准的mAb均由哺乳动物细胞系产生，所述哺乳动物细胞系分泌具有与其人对应物相似但不相同的糖基化结构的mAb。mAb的糖基化影响其与杀死抗体靶向细胞的免疫效应细胞的相互作用（2-6）。在这里，我们证明了具有特定的人N-聚糖结构的人抗体可以在酵母毕赤酵母的糖工程化株系中产生，并且可以通过产生特定的糖型来优化抗体介导的效应子功能。糖工程化的巴斯德毕赤酵母为生产具有人N-糖基化的重组抗体提供了通用平台。
As the fastest growing class of therapeutic proteins, monoclonal antibodies (mAbs) represent a major potential drug class(1). Human antibodies are glycosylated in their native state and all clinically approved mAbs are produced by mammalian cell lines, which secrete mAbs with glycosylation structures that are similar, but not identical, to their human counterparts. Glycosylation of mAbs influences their interaction with immune effector cells that kill antibody-targeted cells(2-6). Here we demonstrate that human antibodies with specific human N-glycan structures can be produced in glycoengineered lines of the yeast Pichia pastoris and that antibody-mediated effector functions can be optimized by generating specific glycoforms. Glycoengineered P. pastoris provides a general platform for producing recombinant antibodies with human N-glycosylation.