Schellenberg Jana, Nagraik Tamanna, Wohlenberg Ole Jacob, Ruhl Sebastian, Bahnemann Janina, Scheper Thomas, Solle Dörte
Institut für Technische Chemie Leibniz Universität Hannover Hannover Germany.
Field Application Specialist - Cell Culture Technologies Sartorius Stedim Biotech GmbH Göttingen Germany.
Eng Life Sci. 2022 Feb 24;22(5):427-436. doi: 10.1002/elsc.202100062. eCollection 2022 May.
Monoclonal antibodies (mAbs) are of great interest to the biopharmaceutical industry due to their widely used application as human therapeutic and diagnostic agents. As such, mAb require to exhibit human-like glycolization patterns. Therefore, recombinant Chinese hamster ovary (CHO) cells are the favored production organisms; many relevant biopharmaceuticals are already produced by this cell type. To optimize the mAb yield in CHO DG44 cells a corelation between stress-induced cell size expansion and increased specific productivity was investigated. CO and macronutrient supply of the cells during a 12-day fed-batch cultivation process were tested as stress factors. Shake flasks (500 mL) and a small-scale bioreactor system (15 mL) were used for the cultivation experiments and compared in terms of their effect on cell diameter, integral viable cell concentration (IVCC), and cell-specific productivity. The achieved stress-induced increase in cell-specific productivity of up to 94.94.9%-134.4% correlates to a cell diameter shift of up to 7.34 μm. The highest final product titer of 4 g/L was reached by glucose oversupply during the batch phase of the process.
单克隆抗体（mAb）作为人类治疗和诊断试剂被广泛应用，因此受到生物制药行业的极大关注。正因如此，单克隆抗体需要呈现出类似人类的糖基化模式。所以，重组中国仓鼠卵巢（CHO）细胞是首选的生产生物体；许多相关生物制药已经由这种细胞类型生产。为了优化CHO DG44细胞中单克隆抗体的产量，研究了应激诱导的细胞大小扩张与特定生产力提高之间的相关性。在为期12天的补料分批培养过程中，测试了细胞的CO和常量营养素供应作为应激因素。使用摇瓶（500 mL）和小型生物反应器系统（15 mL）进行培养实验，并比较它们对细胞直径、活细胞总数（IVCC）和细胞比生产力的影响。所实现的应激诱导细胞比生产力提高高达94.9%-134.4%，这与细胞直径最多7.34μm的变化相关。在该过程的分批阶段通过过量供应葡萄糖达到了最高终产物滴度4 g/L。
