Effect of temperature shift on levels of acidic charge variants in IgG monoclonal antibodies in Chinese hamster ovary cell culture

Kishishita, Shohei; Nishikawa, T; Shinoda, Yasuharu; Nagashima, Hiroaki; Okamoto, Hiroshi; Takuma, Shinya; Aoyagi, Haruhiko

doi:10.1016/j.jbiosc.2014.10.028

Cited by 31 publications

(21 citation statements)

References 32 publications

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“…Based on the results from ambr15 TM , the pH and DO setpoints ([6.75 and 30 %) used in the CFB-1 process were found to be appropriate for the cell line used. Temperature shift to lower levels, though proven to be effective in slowing down cell metabolism, including lactate production in mammalian cell cultures, has been found to negatively impact the specific productivity of the cell line used (data not shown), similar to previously reported cell lines where cell-specific productivity reduced at lower temperature [36][37][38]. Thus, temperature shift was not attempted in the study.…”

Section: Impact Of Control Strategy On Lactate Metabolismsupporting

confidence: 78%

“…The higher acidic variants in the galactose condition could have been caused by the low culture viability, where lysed intracellular contents may impact the acidic species [35]. Strategies in improving cell viability, such as temperature downshift, have been found to be effective in reducing acidic variants [36]. The higher acidic variants in the fructose condition and lower basic variants in the maltose condition are likely directly due to the type of sugar used in the process.…”

Section: Impact Of Medium Components On Lactate Metabolismmentioning

confidence: 99%

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Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Hoshan

Chen

2016

Bioprocess Biosyst Eng

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In this study, we discussed the development and optimization of an intensified CHO culture process, highlighting medium and control strategies to improve lactate metabolism. A few strategies, including supplementing glucose with other sugars (fructose, maltose, and galactose), controlling glucose level at <0.2 mM, and supplementing medium with copper sulfate, were found to be effective in reducing lactate accumulation. Among them, copper sulfate supplementation was found to be critical for process optimization when glucose was in excess. When copper sulfate was supplemented in the new process, two-fold increase in cell density (66.5 ± 8.4 × 10(6) cells/mL) and titer (11.9 ± 0.6 g/L) was achieved. Productivity and product quality attributes differences between batch, fed-batch, and concentrated fed-batch cultures were discussed. The importance of process and cell metabolism understanding when adapting the existing process to a new operational mode was demonstrated in the study.

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Section: Impact Of Control Strategy On Lactate Metabolismsupporting

confidence: 78%

Section: Impact Of Medium Components On Lactate Metabolismmentioning

confidence: 99%

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Hoshan

Chen

2016

Bioprocess Biosyst Eng

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“…Furthermore, the acidic cluster 1 slightly decreased. The effect of the culture temperature on charge variants has been reported previously, correlating a decrease of acidic forms and deamidation of IgGs with decreasing temperature 283,284 . The temperature shift produced lower aggregation, and potentially simplifies the required downstream activities.…”

Section: Discussionsupporting

confidence: 54%

Tailoring recombinant protein quality by rational media design

Brühlmann

Jordan

Hemberger³

et al. 2015

Biotechnology Progress

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Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C‐ & N‐terminal modifications), aggregates, low‐molecular‐weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015

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“…It has been revealed that they can change the binding to proteins or cell membrane targets, thereby affecting the tissue penetration, tissue distribution, and pharmacokinetics of the antibodies[20,55-58]. There is enough evidence in the literature to recommend that the existence of acidic species variants on mAbs can at least have an effect on the resulting protein’s efficacy and function[59-61]. The impacts of the charge variants depend highly on the nature, site, and the amount of post-translational modifications that cause the acidic and basic variants’ formation[62].…”

Section: Introductionmentioning

confidence: 99%

“…Reducing the temperature and accelerating the temperature shift time considerably decrease the acidic charge variant amount[61]. In a study, Zhang et al .…”

Section: Introductionmentioning

confidence: 99%

Main Quality Attributes of Monoclonal Antibodies and Effect of Cell Culture Components

Torkashvand

Vaziri

2017

IBJ

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The culture media optimization is an inevitable part of upstream process development in therapeutic monoclonal antibodies (mAbs) production. The quality by design (QbD) approach defines the assured quality of the final product through the development stage. An important step in QbD is determination of the main quality attributes. During the media optimization, some of the main quality attributes such as glycosylation pattern, charge variants, aggregates, and low-molecular-weight species could be significantly altered. Here, we provide an overview of how cell culture medium components affect the main quality attributes of the mAbs. Knowing the relationship between the culture media components and the main quality attributes could be successfully utilized for rational optimization of mammalian cell culture media for industrial mAbs production.

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Effect of temperature shift on levels of acidic charge variants in IgG monoclonal antibodies in Chinese hamster ovary cell culture

Cited by 31 publications

References 32 publications

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Improving lactate metabolism in an intensified CHO culture process: productivity and product quality considerations

Tailoring recombinant protein quality by rational media design

Main Quality Attributes of Monoclonal Antibodies and Effect of Cell Culture Components

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