Factors affecting the quality of therapeutic proteins in recombinant Chinese hamster ovary cell culture

Ha, Tae Kwang; Kim, Dong-Il; Kim, Che Lin; Grav, Lise Marie; Lee, Gyun Min

doi:10.1016/j.biotechadv.2021.107831

Cited by 34 publications

(30 citation statements)

References 214 publications

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“…However, maintaining high productivity of cells and quality attributes of protein is still a challenge. Therefore, fed-batch culture has shifted from the high-yield recombinant protein merely to the dual goals of high-yield and high-quality production (Ha et al 2022 ).…”

Section: Cho Cell Culturementioning

confidence: 99%

“…Nutrient supplementation and metabolic byproducts accumulation are able to increase extracellular osmolality at the late stages of culture in fed-batch culture (Alhuthali et al 2021 ). Both nutrient and alkaline supplemented can increase the osmolality of the culture environment (Ha et al 2022 ). In fed-batch process, NaCl maintained high osmolality.…”

Section: Osmolalitymentioning

confidence: 99%

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Progress in fed-batch culture for recombinant protein production in CHO cells

Lin

et al. 2023

Appl Microbiol Biotechnol

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Nearly 80% of the approved human therapeutic antibodies are produced by Chinese Hamster Ovary (CHO) cells. To achieve better cell growth and high-yield recombinant protein, fed-batch culture is typically used for recombinant protein production in CHO cells. According to the demand of nutrients consumption, feed medium containing multiple components in cell culture can affect the characteristics of cell growth and improve the yield and quality of recombinant protein. Fed-batch optimization should have a connection with comprehensive factors such as culture environmental parameters, feed composition, and feeding strategy. At present, process intensification (PI) is explored to maintain production flexible and meet forthcoming demands of biotherapeutics process. Here, CHO cell culture, feed composition in fed-batch culture, fed-batch culture environmental parameters, feeding strategies, metabolic byproducts in fed-batch culture, chemostat cultivation, and the intensified fed-batch are reviewed. Key points • Fed-batch culture in CHO cells is reviewed. • Fed-batch has become a common technology for recombinant protein production. • Fed batch culture promotes recombinant protein production in CHO cells.

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Section: Cho Cell Culturementioning

confidence: 99%

Section: Osmolalitymentioning

confidence: 99%

Progress in fed-batch culture for recombinant protein production in CHO cells

Lin

et al. 2023

Appl Microbiol Biotechnol

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“…The production of recombinant antibody drugs is mostly achieved by constructing expression vectors in vitro through genetic engineering technology. Given that recombinant antibodies often need to undergo a series of post-translational modifications (such as glycosylation modification), folding, and correct cleavage, antibody drugs with biological activity and low immunogenicity can be produced, therefore, mammalian cells have become the dominant system for the production of recombinant antibodies, especially for full-length monoclonal antibodies ( Hussain et al, 2021 ; Kim et al, 2021 ; Ha et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Zhang

Shan

Liang

et al. 2022

Front. Bioeng. Biotechnol.

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Recombinant antibodies are rapidly developing therapeutic agents; approximately 40 novel antibody molecules enter clinical trials each year, most of which are produced from Chinese hamster ovary (CHO) cells. However, one of the major bottlenecks restricting the development of antibody drugs is how to perform high-level expression and production of recombinant antibodies. The high-efficiency expression and quality of recombinant antibodies in CHO cells is determined by multiple factors. This review provides a comprehensive overview of several state-of-the-art approaches, such as optimization of gene sequence of antibody, construction and optimization of high-efficiency expression vector, using antibody expression system, transformation of host cell lines, and glycosylation modification. Finally, the authors discuss the potential of large-scale production of recombinant antibodies and development of culture processes for biopharmaceutical manufacturing in the future.

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“…The Chinese hamster ovary (CHO)-derived immortalized cells originally established by Puck et al [ 16 ] are currently the most frequently used line for biopharmaceutical production [ 17 ]. Among them, decoding of the entire genome sequence [ 18 , 19 ], omics analyses including transcriptomic [ 20 ] and proteomic [ 21 , 22 ] analyses, and karyotype analysis [ 23 ] have been extensively studied in CHO-K1 cells.…”

Section: Introductionmentioning

confidence: 99%

Novel cell lines derived from Chinese hamster kidney tissue

Kawabe

Kamihira

2022

PLoS ONE

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Immortalized kidney cell lines are widely used in basic and applied research such as cell permeability tests and drug screening. Although many cell lines have been established from kidney tissues, the immortalization process has not been clarified in these cell lines. In this study, we analyzed the phenotypic changes that occurred during the immortalization of kidney cells derived from Chinese hamster tissue in terms of karyotype and gene expression profiles. In the newly established cell line, designated as CHK-Q, gene expression profiles at each stage of the immortalization process and during the adaptation to serum-free conditions were analyzed by DNA microarray. Renal stem cell markers CD24 and CD133 were expressed in CHK-Q cells, suggesting that CHK-Q cells were transformed from renal stem cells. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to identify the pathways of upregulated and downregulated genes revealed that the immortalization of CHK-Q cells was associated with increased fluctuations in the expression of specific proto-oncogenes. Karyotype analysis of spontaneously immortalized CHK-Q cells indicated that CHK-Q chromosomes had a typical modal number of 23 but possessed slight chromosomal abnormalities. In this study, we investigated the mechanism of cell environmental adaptation by analyzing gene expression behavior during the immortalization process and serum-free adaptation. CHK-Q cells are applicable to the fields of biotechnology and biomedical science by utilizing their characteristics as kidney-derived cells.

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Factors affecting the quality of therapeutic proteins in recombinant Chinese hamster ovary cell culture

Cited by 34 publications

References 214 publications

Progress in fed-batch culture for recombinant protein production in CHO cells

Progress in fed-batch culture for recombinant protein production in CHO cells

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Novel cell lines derived from Chinese hamster kidney tissue

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