Li Huijuan, Sethuraman Natarajan, Stadheim Terrance A, Zha Dongxing, Prinz Bianka, Ballew Nicole, Bobrowicz Piotr, Choi Byung-Kwon, Cook W James, Cukan Michael, Houston-Cummings Nga Rewa, Davidson Robert, Gong Bing, Hamilton Stephen R, Hoopes Jack P, Jiang Youwei, Kim Nam, Mansfield Renee, Nett Juergen H, Rios Sandra, Strawbridge Rendall, Wildt Stefan, Gerngross Tillman U
GlycoFi Inc. 21 Lafayette Street, Lebanon, New Hampshire 03766, USA.
Nat Biotechnol. 2006 Feb;24(2):210-5. doi: 10.1038/nbt1178. Epub 2006 Jan 22.
As the fastest growing class of therapeutic proteins, monoclonal antibodies (mAbs) represent a major potential drug class. 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. 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.
作为治疗性蛋白质中增长最快的类别，单克隆抗体（mAb）代表了一类主要的潜在药物。人抗体在其天然状态下是糖基化的，所有临床批准的单克隆抗体均由哺乳动物细胞系产生，这些细胞系分泌的单克隆抗体具有与人类对应物相似但不完全相同的糖基化结构。单克隆抗体的糖基化会影响它们与杀死抗体靶向细胞的免疫效应细胞的相互作用。在这里，我们证明了具有特定人N-聚糖结构的人抗体可以在酵母毕赤酵母的糖工程化细胞系中产生，并且可以通过产生特定的糖型来优化抗体介导的效应功能。糖工程化的毕赤酵母为生产具有人N-糖基化的重组抗体提供了一个通用平台。
