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Enhanced Productivity of NSO Cells in Fed-Batch Culture with Cholesterol Nanoparticle Supplementation

机译:补充胆固醇纳米颗粒在分批补料培养中提高了NSO细胞的生产力

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摘要

NSO cells are an important industrial cell line for the production of therapeutic monoclonal antibodies. Culturing these cells is challenging because they are cholesterol auxotrophs, and providing cholesterol to the cells is hampered by the low solubility of lipids in aqueous medium. Limited loading capacity, precipitation, instability, and toxicity are associated with traditional delivery methods that involve solvents or carrier molecules. In this work, nanoparticle cholesterol mixtures (NCM) were produced by electrohydrodynamic spraying and added directly to a cholesterol auxotroph NSO cell line. Compared to a cholesterol-cyclodex-trin solution and a commercial proprietary cholesterol solution, SyntheChol? NSO supplement, NCM is significantly less cytotoxic. In the fed batch cell culture process, product titer was increased by 32% when the NCM supplement replaced SyntheChol NSO supplement. An even greater product titer improvement, 64%, was achieved when both NCM and SyntheChol? NSO supplements were used in the fed-batch process.
机译:NSO细胞是用于生产治疗性单克隆抗体的重要工业细胞系。培养这些细胞具有挑战性,因为它们是胆固醇营养缺陷型,并且脂质在水性介质中的低溶解性阻碍了向细胞提供胆固醇。有限的负载能力,沉淀,不稳定性和毒性与涉及溶剂或载体分子的传统递送方法有关。在这项工作中,纳米粒子胆固醇混合物(NCM)是通过电动流体动力喷雾产生的,并直接添加到胆固醇营养缺陷型NSO细胞系中。与胆固醇-环糊精-Trin溶液和商业专有的胆固醇溶液相比,SyntheChol?补充NSO后,NCM的细胞毒性明显降低。在补料分批细胞培养过程中,当NCM补充剂替代SyntheChol NSO补充剂时,产品效价提高了32%。 NCM和SyntheChol?可使产品滴度进一步提高64%。在分批补料过程中使用了NSO补充剂。

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