Methods for reducing the ammonia in hybridoma cell cultures

Capiaumont, J.; Legrand, Chantal; Carbonell, Denysha; Dousset, B.; Belleville, F.; Nabet, P

doi:10.1016/0168-1656(94)00142-y

Cited by 26 publications

(11 citation statements)

References 22 publications

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“…A number of methods have been introduced to reduce ammonia production in culture including perfusion (Butler et al, 1983), ion-exchange resins, and gas-permeable hydrophobic membranes (Capiaumont et al, 1995). However, the most efficient and cost-effective strategy of controlling ammonia formation is by preventing its production in the first place.…”

Section: Introductionmentioning

confidence: 99%

The adaptation of bhk cells to a non-ammoniagenic glutamate-based culture medium

Christie

Butler

1999

Biotechnol. Bioeng.

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Section: Introductionmentioning

confidence: 99%

The adaptation of bhk cells to a non-ammoniagenic glutamate-based culture medium

Christie

Butler

1999

Biotechnol. Bioeng.

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“…Research on the characterization and improvement of these types of process has been carried out for many years [4,5,6,7,8,9,10,11,12,13,14,15], but significant improvements are still possible [16,17,18].…”

mentioning

confidence: 99%

Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis

Frahm

Lane

Märkl

et al. 2003

Bioprocess and Biosystems Engineering

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Both conventional and genetic engineering techniques can significantly improve the performance of animal cell cultures for the large-scale production of pharmaceutical products. In this paper, the effect of such techniques on cell yield and antibody production of two NS0 cell lines is presented. On the one hand, the effect of fed-batch cultivation using dialysis is compared to cultivation without dialysis. Maximum cell density could be increased by a factor of approximately 5-7 by dialysis fed-batch cultivation. On the other hand, suppression of apoptosis in the NS0 cell line 6A1 bcl-2 resulted in a prolonged growth phase and a higher viability and maximum cell density in fed-batch cultivation in contrast to the control cell line 6A1 (100)3. These factors resulted in more product formation (by a factor of approximately 2). Finally, the adaptive model-based OLFO controller, developed as a general tool for cell culture fed-batch processes, was able to control the fed-batch and dialysis fed-batch cultivations of both cell lines.

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“…Glutamine substitution by glutamate significantly decreased ammonia accumulation in murine hybridoma cell cultures as well. However, cell growth and monoclonal antibody production were reduced by approximately 30% by glutamine substitution [71]. In human embryonic kidney 293 (HEK293) cell cultures future science group Review Ha & Lee for recombinant adenovirus production, glutamine substitution by glutamate significantly reduced ammonia accumulation and resulted in a 1.8-fold increase in adenovirus volumetric productivity [72].…”

Section: Glutamine Substitution By Lesser Ammonia Producing Substratesmentioning

confidence: 99%

“…Maximal yield of poliovirus production [68] HeLa -Glutamate Growth improvement [69] Vero, McCoy, BHK -Either glutamate and alpha-ketoglutarate 70% reduction of ammonia accumulation [70] Hybridoma IgG1 Glutamate Reduction of ammonia accumulation (<0.5 mM) [71] CHO tPA Glutamate Reduction of ammonia and lactate, increase of tPA production rate [73] CHO tPA Glutamate Higher cell concentration, lower production of byproducts [75] CHO tPA Glutamate Reduction of ammonia and lactate, increase of tPA production rate [74] HEK293 Adenovirus Glutamate…”

Section: Hela Poliovirus Glutamatementioning

confidence: 99%

Glutamine substitution: the role it can play to enhance therapeutic protein production

Ha¹,

Lee²

2015

Pharmaceutical Bioprocessing

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The biopharmaceutical market is driven by the steady increase in demand for therapeutic proteins produced in mammalian cells. Glutamine is a main nitrogen source and also a main energy source with glucose in mammalian cell cultures for therapeutic protein production. As a result of glutamine metabolism and the natural decomposition of glutamine, ammonia, which is known to negatively affect cell growth, protein production and sialylation of recombinant glycoprotein, is necessarily accumulated in a culture medium. This review highlights the current strategies and achievements in overcoming the negative effect of ammonia through the glutamine substitution by less ammoniagenic substrates, such as glutamate, pyruvate and α-ketoglutarate.

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Methods for reducing the ammonia in hybridoma cell cultures

Cited by 26 publications

References 22 publications

The adaptation of bhk cells to a non-ammoniagenic glutamate-based culture medium

The adaptation of bhk cells to a non-ammoniagenic glutamate-based culture medium

Improvement of a mammalian cell culture process by adaptive, model-based dialysis fed-batch cultivation and suppression of apoptosis

Glutamine substitution: the role it can play to enhance therapeutic protein production

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