Metabolite Profiling of Recombinant CHO Cells: Designing Tailored Feeding Regimes That Enhance Recombinant Antibody Production
Metabolite Profiling of Recombinant CHO Cells: Designing Tailored Feeding Regimes That Enhance Recombinant Antibody Production
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DOI：
10.1002/bit.23269
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发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Dickson, Alan J.
中科院分区：
文献类型：
--
作者：
Sellick, Christopher A.;Croxford, Alexandra S.;Dickson, Alan J.
中国仓鼠卵巢（CHO）细胞是重组治疗性蛋白的商业表达的主要平台。从表达平台获得最大产量需要最佳的细胞培养基（和相关的营养补料）。我们已使用代谢物分析来确定表达重组IgG 4抗体的CHO细胞系生产过程中细胞内和细胞外代谢物的平衡。使用这种代谢物分析方法，可以确定营养限制，这是抗体生产的瓶颈，并随后开发一种简单的喂养方案，以缓解这些代谢瓶颈。这种基于代谢物分析的策略用于设计靶向的低成本营养补料，其使细胞生物量增加35%并使抗体滴度加倍。这种方法具有在非专业实验室中使用的潜力，可以普遍应用于商业上重要的生物药物生产的优化。Biotechnol. Bioeng. 2011; 108：3025-3031。(C)2011 Wiley Periodicals，Inc.
Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the balance of intracellular and extracellular metabolites during the production process of a CHO cell line expressing a recombinant IgG4 antibody. Using this metabolite profiling approach, it was possible to identify nutrient limitations, which acted as bottlenecks for antibody production, and subsequently develop a simple feeding regime to relieve these metabolic bottlenecks. This metabolite profiling-based strategy was used to design a targeted, low cost nutrient feed that increased cell biomass by 35% and doubled the antibody titer. This approach, with the potential for utilization in non-specialized laboratories, can be applied universally to the optimization of production of commercially important biopharmaceuticals. Biotechnol. Bioeng. 2011; 108: 3025-3031. (C) 2011 Wiley Periodicals, Inc.