Improved process robustness, product quality and biological efficacy of an anti-CD52 monoclonal antibody upon pH shift in Chinese hamster ovary cell perfusion culture

Zheng, Chen; Zhuang, Chao; Chen, Yantian; Fu, Qiang; Qian, Hui; Wang, Yanchao; Qin, Jinyan; Wu, Xiang; Qi, Nianmin

doi:10.1016/j.procbio.2017.11.013

Cited by 23 publications

(13 citation statements)

References 37 publications

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“…This leads to the assumption, that a change during the cultivation generates more cell stress than constant cultivation conditions. Similar effects of a pH shift can be found for the production of an anti‐CD52 mAb in CHO cells [33]. Additionally, lower CO 2 flow rates were required to maintain a higher pH of 7.3 which conversely confirms that CO 2 supply reduction leads to pH changes in the culture medium (Supporting Information, Figure S1).…”

Section: Resultssupporting

confidence: 74%

“…This leads to the assumption, that a change during the cultivation generates more cell stress than constant cultivation conditions. Similar effects of a pH shift can be found for the production of an anti-CD52 mAb in CHO cells [33]. Additionally, lower CO 2 flow F I G U R E 3 VCC and product concentration (mAb) for pH_0 and pH_5 with pH shifts compared to the pH_Reference (A).…”

Section: Investigation Of Ph Shifts As a Response To Co 2 Limitationsupporting

confidence: 56%

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Stress‐induced increase of monoclonal antibody production in CHO cells

Schellenberg

Nagraik

Wohlenberg

et al. 2022

Engineering in Life Sciences

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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 2 and macronutrient supply of the cells during a 12-day fedbatch 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 stressinduced 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.

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Section: Resultssupporting

confidence: 74%

“…This leads to the assumption, that a change during the cultivation generates more cell stress than constant cultivation conditions. Similar effects of a pH shift can be found for the production of an anti-CD52 mAb in CHO cells [33]. Additionally, lower CO 2 flow F I G U R E 3 VCC and product concentration (mAb) for pH_0 and pH_5 with pH shifts compared to the pH_Reference (A).…”

Section: Investigation Of Ph Shifts As a Response To Co 2 Limitationsupporting

confidence: 56%

Stress‐induced increase of monoclonal antibody production in CHO cells

Schellenberg

Nagraik

Wohlenberg

et al. 2022

Engineering in Life Sciences

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“…When the carbon source content is reduced, cell activity decreases significantly, and the cell metabolism is the main consumption of lactic acid. In another study, the pH value decreased from 7.15 to 6.85 on the 9th day in the CHO perfusion culture, increasing the cell density and longevity, and improving the glycation and potency of mAb, while maintaining the cell activity [23] . Briefly, the cell culture process relies on the pH value.…”

Section: Ph Valuementioning

confidence: 95%

Research Update on Bioreactors Used in Tissue Engineering

Wang

Deng

et al. 2021

J. Shanghai Jiaotong Univ. (Sci.)

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Owing to the paucity of donor organs and their acute rejection by the immune system after transplantation, advanced organ failure is one of the major challenges faced by the medical community. Static culturing used for synthesising tissues and organs cannot simulate the in vivo mechanical and biochemical signals; therefore, such artificial organs fail to maintain effective functional activity following transplantation. Tissue engineering can overcome these hurdles by successfully enabling regeneration of tissues and organs in vitro. Bioreactors are pivotal in the development and generation of engineered biological products. They simulate the in vivo microenvironment of tissue growth while also providing various mechanical stimuli and biochemical signals to stem cells to effectively generate transplantable organs or tissues. Various designs and types of bioreactors, their applications, and future research prospects are summarised, which promote functional tissue engineering.

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“…Optimizing the cultivation step is critical due to its impact on the overall production time and cost . Various technologies have been developed to improve production efficiency, including continuous production, temperature shifts, , pH shifts, − and modifying host cell lines …”

Section: Introductionmentioning

confidence: 99%

Hybrid Modeling of CHO Cell Cultivation in Monoclonal Antibody Production with an Impurity Generation Module

Okamura

Badr

Murakami³

et al. 2022

Ind. Eng. Chem. Res.

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Representative cultivation models are needed for designing efficient monoclonal antibody (mAb) production processes. Simple Monod-type kinetic models could fail to capture changes at different phases and conditions. Current models rarely account for process-related impurities, which hinders optimizing integrated processes. A three-module hybrid approach is thus introduced here. Module 1 is a kinetic metabolism model until cell death based on Monod-type equations. Module 2 is a data-driven module for updating parameters based on system dynamics and changes in cultivation conditions. Module 3 proposes a kinetic model for the generation of host cell proteins and DNA. The model is applied to newly established high-performance CHO cell lines and is validated with experiments at different operating conditions. The adopted modular approach helps identify weak model links, which can be corrected via the data-driven module. The proposed model combines accuracy and simplicity for design and control applications of cultivation processes considering quality aspects.

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Improved process robustness, product quality and biological efficacy of an anti-CD52 monoclonal antibody upon pH shift in Chinese hamster ovary cell perfusion culture

Cited by 23 publications

References 37 publications

Stress‐induced increase of monoclonal antibody production in CHO cells

Stress‐induced increase of monoclonal antibody production in CHO cells

Research Update on Bioreactors Used in Tissue Engineering

Hybrid Modeling of CHO Cell Cultivation in Monoclonal Antibody Production with an Impurity Generation Module

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