Gamma-interferon production and quality in stoichiometric fed-batch cultures of Chinese hamster ovary (CHO) cells under serum-free conditions

Xie, Liangzhi; Nyberg, Gregg; Gu, Xuejun; Li, Hanyuan; Möllborn, Fredrik; Wang, Daniel I. C.

doi:10.1002/(sici)1097-0290(19971205)56:5<577::aid-bit11>3.0.co;2-9

Cited by 56 publications

(29 citation statements)

References 16 publications

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“…A stoichiometric model for mammalian cell growth and monoclonal antibody expression has been developed, and successfully utilized to optimize glucose, glutamine and amino acid concentrations in cell culture media and supplements, resulting in significant improvements in cell density and product titer . Although initially developed for hybridoma cultures, this stoichiometric model has also been applied to a CHO cell process for recombinant Gamma‐interferon expression, resulting in improved growth, production and glycosylation of the final product, with reduced accumulation of metabolic byproducts in the culture medium . These studies demonstrate the general applicability of stoichiometric models for medium optimization.…”

Section: Optimization Of Growth Media For Recombinant Protein Expressionmentioning

confidence: 93%

“…Since these early achievements, the evolution of serum‐free cell culture media has continued through development and optimization efforts aimed at supporting higher cell densities, viability and recombinant protein titer. Research groups at the Massachusetts Institute of Technology and the University of Minnesota pioneered the use of stoichiometric analysis of cell growth and nutrient utilization to design basal and feed media formulations to feed according to nutrient demand, thereby preventing depletion of key nutrients while minimizing accumulation of toxic metabolic waste . Further optimization of CHO cell culture media and process parameters by leading teams in the biopharmaceutical industry, specifically aimed at commercial manufacturing of mAbs and other recombinant proteins, has resulted in dramatic increases in cell density and protein expression, with titers reaching more than 10 g/L in some cases .…”

Section: Historical Evolution Of Media Formulations To Support Mammalmentioning

confidence: 99%

“…The stoichiometric analyses mentioned previously which defined key metabolic and nutrient demands involved in animal cell growth and protein expression, and the eventual application of a stoichiometric model to a CHO cell culture process led the way for the future development and application of MFA for CHO cells. MFA has been used to model central metabolism in CHO cells, and has been applied to CHO cell culture processes to gain insight into glucose and nitrogen utilization, and lactate consumption .…”

Section: Optimization Of Growth Media For Recombinant Protein Expressionmentioning

confidence: 99%

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Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Ritacco

Khetan

2018

Biotechnology Progress

172

138

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The culture of Chinese Hamster Ovary (CHO) cells for modern industrial applications, such as expression of recombinant proteins, requires media that support growth and production. Such media must support high viable cell densities while also stimulating the synthesis and extracellular transport of biologic products. Early media development efforts in this area yielded basic formulations to sustain growth, viability, and cellular function, albeit comprising animal sourced components, and complex constituents used in batch culture mode. Subsequent improvements included the development of serum‐free and chemically defined (CD) media, the identification of critical nutrients, growth factors, and potentially inhibitory or toxic cellular metabolites, and the use of fed‐batch and perfusion culture techniques to optimize nutrient delivery while minimizing accumulation of unwanted waste products. This review is comprised of sections covering milestones in the evolution of mammalian cell culture media, nutrient composition and formulation requirements, optimization strategies, consistency and scalability of powder and liquid media preparation for industrial applications, and key recent advances driving progress in CHO cell culture medium design and development. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1407–1426, 2018

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Section: Optimization Of Growth Media For Recombinant Protein Expressionmentioning

confidence: 93%

Section: Historical Evolution Of Media Formulations To Support Mammalmentioning

confidence: 99%

Section: Optimization Of Growth Media For Recombinant Protein Expressionmentioning

confidence: 99%

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Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Ritacco

Khetan

2018

Biotechnology Progress

172

138

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“…human macrophage colony stimulating factor (Sinacore et al, 1996), human clotting factor IX (Sinacore et al, 1996), γ-interferon Xie et al, 1997), and the humanized antibody CAMPATH-1H (Keen and Rapson, 1995). However, the increase in productivity under serumsupplemented conditions was offset by lower cell densities of confluent cultures in the presence of FCS (usually around 4·10 4 cells/cm 2 ).…”

Section: Production Of Atiii Under Serum-free Conditionsmentioning

confidence: 99%

Serum- and protein-free media formulations for the Chinese hamster ovary cell line DUKXB11

Schröder

Matischak

Friedl

2004

Journal of Biotechnology

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Citation for published item:hr¤ oderD wF nd w tis h kD uF nd priedlD F @PHHRA 9 erumE nd proteinEfree medi formul tions for the ghinese h mster ov ry ell line h u fIIF9D tourn l of iote hnologyFD IHV @QAF ppF PUWEPWPF Further information on publisher's website: httpXGGdxFdoiForgGIHFIHITGjFj iote FPHHQFIPFHHS Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractThe production of therapeutic proteins in mammalian cell lines is of outstanding importance. The maintenance of most mammalian cell lines in culture requires the addition of serum to the culture medium.The elimination of serum from mammalian cell culture is desirable since serum is expensive and a source of contaminants, e.g. viruses, mycoplasma or prions. Here we describe the composition of serum-and protein-free media for the Chinese hamster ovary (CHO) cell line DUKXB11. The serum-free formulation supports excellent growth of CHO DUKXB11 cells at low (23 cells/cm 2 ) and high (2·10 4 cells/cm 2 ) seeding densities characterized by a generation time of 10 -12 h, and, after addition of 0.2% pluronic F-68, the growth of a recombinant suspension cell line derived from DUKXB11. In addition, this formulation also allowed us to adapt recombinant cell lines expressing various amounts of human antithrombin ATIII (ATIII)to serum-free conditions. Secretion of ATIII was readily observed in the serum-free medium. Minor changes to the serum-free formulation resulted in a protein free formulation that supported growth of CHO DUKXB11 cells, growth of recombinant CHO cells expressing ATIII, and production of ATIII. Key wordsChinese hamster ovary cells, serum-free medium, protein-free medium, recombinant protein production,

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“…It has been reported that fed‐batch strategies, which uses low glucose or glutamine, can lead to significant changes to glycoprotein quality (Kochanowski et al, 2008; Wong et al, 2005). Although heterogeneity changes in recombinant glycoprotein N ‐glycosylation during culture have been examined in various studies (Hooker et al, 1995; Wong et al, 2005; Xie et al, 1997; Yang and Butler, 2000; Yuk and Wang, 2002), the changes in the expression of glycosylation‐related genes have not been examined extensively.…”

Section: Introductionmentioning

confidence: 99%

Reactive blending approach to modify spin‐coated epoxy film: Part II. Crosslinking kinetics

Turunen

Laurila

Kivilahti

2006

J of Applied Polymer Sci

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Kinetics of the reactive blending of epoxy with a four-armed -caprolactone-based carboxylic acid end-functionalized oligomer was analyzed with a modelfree approach. The employment of a dual catalyst system ensured high density of crosslinking in the blends and minimized phase separation even when comparatively high concentration of the oligomer was incorporated. The two reactions were examined separately before analysis of the dual-catalyzed system. The apparent activation energy of the single-catalyzed reactions could be seen to fall into three regimes. It is proposed that regime I is due to reaction control, the middle part (II) to mass transport, and the high conversion tail (III) to structural control. The results of a thermal analysis carried out on the crosslinked samples corresponded well with the findings of the kinetic analysis. The combined kinetic and thermal results can be used in optimization of the crosslinking process.

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Gamma-interferon production and quality in stoichiometric fed-batch cultures of Chinese hamster ovary (CHO) cells under serum-free conditions

Cited by 56 publications

References 16 publications

Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Cell culture media for recombinant protein expression in Chinese hamster ovary (CHO) cells: History, key components, and optimization strategies

Serum- and protein-free media formulations for the Chinese hamster ovary cell line DUKXB11

Reactive blending approach to modify spin‐coated epoxy film: Part II. Crosslinking kinetics

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