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The molecular weight and concentration of dextran sulfate affect cell growth and antibody production in CHO cell cultures

机译：硫酸葡聚糖的分子量和浓度会影响CHO细胞培养物中的细胞生长和抗体产生

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To investigate the effect of dextran sulfate (DS), a widely used anti-aggregation agent, on cell growth and monoclonal antibody (mAb) production including the quality attributes, DS with the three different MWs (4,000 Da, 15,000 Da, and 40,000 Da) at various concentrations (up to 1 g/L) was added to suspension cultures of two different recombinant CHO (rCHO) cell lines producing mAb, SM-0.025 and CS13-1.00. For both cell lines, the addition of DS, regardless of the MW and concentration of DS used, improved cell growth and viability in the decline phase of growth. However, it increased mAb production only in the CS13-1.00 cells. Among the three different MWs, 40,000 Da DS was most effective in attenuating cell aggregation during the cultures of CS13-1.00 cells, and showed the highest maximum mAb concentration. For SM-0.025 cells, it significantly decreased specific mAb productivity, particularly at a high concentration of DS. Overall, DS addition did not negatively affect the quality attributes of mAbs (aggregation, charge variation, and glycosylation), though its efficacy on mAb quality depended on the MW and concentration of DS and cell lines. For both cell lines, the addition of DS did not affect N-glycosylation of mAbs and decreased basic charge variants in mAbs. For CS13-1.00 cells, the mAb monomer increased with the addition of 40,000 Da DS at 0.3-1.0 g/L. Taken together, to maximize the beneficial effect of DS addition on mAb production, the optimal MW and concentration of DS should be determined for each specific rCHO cell line. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1113-1122, 2016
机译：为了研究广泛使用的抗聚集剂硫酸右旋糖酐（DS）对细胞生长和单克隆抗体（mAb）产生的影响，包括质量属性，具有三种不同分子量（4,000 Da，15,000 Da和40,000 Da）的DS ）将各种浓度（最高达1 g / L）的）加入产生mAb，SM-0.025和CS13-1.00的两种不同重组CHO（rCHO）细胞系的悬浮培养物中。对于两种细胞系，无论使用何种分子量和浓度的DS，DS的添加都能改善细胞生长和生长下降阶段的活力。但是，它仅在CS13-1.00细胞中增加了mAb的产生。在三种不同的MW中，40,000 Da DS在减弱CS13-1.00细胞培养过程中的细胞聚集方面最有效，并且显示出最高的最大mAb浓度。对于SM-0.025细胞，它会显着降低比mAb生产率，尤其是在高浓度的DS下。总体而言，添加DS不会对mAb的质量属性（聚集，电荷变化和糖基化）产生负面影响，尽管其对mAb质量的功效取决于DS和细胞系的分子量和浓度。对于两种细胞系，添加DS均不影响mAb的N-糖基化，也不会降低mAb中的碱性电荷变异体。对于CS13-1.00细胞，mAb单体在0.3-1.0 g / L下添加40,000 Da DS时增加。综上所述，为了最大程度地增加DS添加对mAb产生的有益影响，应该为每种特定的rCHO细胞系确定最佳的MW和DS浓度。 （c）2016美国化学工程师学会生物技术学会。 Prog。，32：1113-1122，2016

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