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>3.3.co;2-z

Cited by 6 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…18,20,21 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. 17 These studies demonstrate the general applicability of stoichiometric models for medium optimization.…”

Section: Experimental Approaches To Medium Optimizationmentioning

confidence: 67%

“…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. [17][18][19][20][21] 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. [22][23][24][25][26][27][28][29][30][31][32] Furthermore, several companies specializing in cell culture media have developed and optimized basal and feed media combinations specifically for recombinant CHO manufacturing processes (ThermoFisher, Waltham, MA, USA, GE Healthcare, Waukesha, WI, USA, MilliporeSigma, St. Louis, MO, USA, Lonza, Basel, Switzerland, Irvine Scientific, Santa Ana, CA, USA).…”

Section: Historical Evolution Of Media Formulations To Support Mammalmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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

show abstract

Section: Experimental Approaches To Medium Optimizationmentioning

confidence: 67%

Section: Historical Evolution Of Media Formulations To Support Mammalmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…This decrease in site occupancy has been observed to correlate with decreased growth and specific productivity (Curling et al, 1990;Hayter et al, 1993). Glucose and glutamine limitation have also been observed to lead to decreased ␥-interferon site occupancy in CHO cultures (Hayter et al, 1992;Nyberg et al, 1999;Xie et al, 1997). In other studies, several lipid-related factors were observed to influence ␥-interferon site occupancy, and specific lipid supplements were found to reduce the deterioration in site occupancy during batch cultures (Jenkins et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator

Andersen¹,

Bridges²,

Gawlitzek³

et al. 2000

Biotechnol. Bioeng.

View full text Add to dashboard Cite

Human tissue-type plasminogen activator (t-PA) contains a variably occupied glycosylation site at Asn-184 in naturally produced t-PA and in t-PA produced in recombinant Chinese hamster ovary (CHO) cells. The presence of an oligosaccharide at this site has previously been shown to reduce specific activity and fibrin binding. In this report, the site occupancy of t-PA is shown to increase gradually over the course of batch and fedbatch CHO cultures. Additional cell culture factors, including butyrate and temperature, are also shown to influence the degree of glycosylation. In each of these cases, conditions with decreased growth rate correlate with increased site occupancy. Investigations using quinidine and thymidine to manipulate the cell cycle distribution of cultures further support this correlation between site occupancy and growth state. Comparison of the cell cycle distribution across the range of cell culture factors investigated shows a consistent relationship between site occupancy and the fraction of cells in the G 0 /G 1 phase of the cell cycle. These results support a correlation between growth state and site occupancy, which fundamentally differs from site occupancy trends previously observed and illustrates the importance of the growth profile of CHO cultures in producing consistently glycosylated recombinant glycoproteins.

show abstract

“…In addition, the influence of the most important metabolite, such as ammonia, on cell growth, extracellular metabolic rates, and antibody *Corresponding author Tel: +86-21-6425-0948 Fax: +86-21-6425-2250 e-mail: wstan@ecust.edu.cn production was well documented on these cell lines [2][3][4]. Researches about process optimization have been focused on solving that critical problem to extend the culture duration as possible [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Responses of GS-NS0 Myeloma cells to osmolality: Cell growth, intracellular mass metabolism, energy metabolism, and antibody production

Zhao

Fan

Wang

et al. 2009

Biotechnol Bioproc E

View full text Add to dashboard Cite

The influence of osmolality on growth, metabolism, and antibody production of mammalian cells has been widely reported in the past. However, more information about the responses of GS-NS0 Myeloma cells to osmolality, especially regarding the intracellular mass and energy metabolism, has not been available in detail. Fed-batch cultures started at different osmolalities in the range of 280~370 mOsm/kg were designed to investigate the effects. As the osmolality and cell status changed during the process, cell performance was evaluated in the comparable periods with similar growth rates, nutrition concentrations, and relatively consistent environments. Metabolic flux analysis indicated most of extra consumed glucose at higher osmolalities flowed into lactate formation pathway. The proportion of glucose flux flowed into glycolysis pathway remained approximately 90% and the need of glucose for biomass synthesis was constantly. Also, more than 88% of the glutamine was used in biomass synthesis and the absolute flux remained constant. The specific consumption rate of glutamine declined significantly when cells were cultured in hypo-osmolality (276 mOsm/kg) and a portion of glutamine was synthesized from glutamate. Furthermore, cells were in the state of high energy production at osmolality of 276 mOsm/kg. More glucose flowed into TCA circle with the high efficiency of energy production to meet the demand. Thus, the IVC, the specific antibody production rate, and maximal antibody concentration in fed-batch culture started at 280 mOsm/kg decreased by 35, 36, and 48% compared to those in the culture started at 330 mOsm/kg. © KSBB hÉóïçêÇëW=dpJkpM=ÅÉääëI=çëãçä~äáíóI=ÅÉää=ÖêçïíÜI=ãÉí~ÄçäáëãI=~åíáÄçÇó=éêçÇìÅíáçå=

show abstract

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

Cited by 6 publications

References 0 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

Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator

Responses of GS-NS0 Myeloma cells to osmolality: Cell growth, intracellular mass metabolism, energy metabolism, and antibody production

Contact Info

Product

Resources

About