Abstract:
:Glycosylation is a key critical quality attribute for monoclonal antibodies and other recombinant proteins because of its impact on effector mechanisms and half-life. In this study, a variety of compounds were evaluated for their ability to modulate glycosylation profiles of recombinant monoclonal antibodies produced in Chinese hamster ovary cells. Compounds were supplemented into the cell culture feed of fed-batch experiments performed with a CHO K1 and a CHO DG44 cell line expressing a recombinant immunoglobulin G1 (IgG1). Experiments were performed in spin tubes or the ambr®15 controlled bioreactor system, and the impact of the compounds at various concentrations was determined by monitoring the glycosylation profile of the IgG and cell culture parameters, such as viable cell density, viability, and titer. Results indicate that the highest impact on mannosylation was achieved through 15 µM kifunensine supplementation leading to an 85.8% increase in high-mannose containing species. Fucosylation was reduced by 76.1% through addition of 800 µM 2-F-peracetyl fucose. An increase of 40.9% in galactosylated species was achieved through the addition of 120 mM galactose in combination with 48 µM manganese and 24 µM uridine. Furthermore, 6.9% increased sialylation was detected through the addition of 30 µM dexamethasone in combination with the same manganese, uridine, and galactose mixture used to increase total galactosylation. Further compounds or combinations of additives were also efficient at achieving a smaller overall glycosylation modulation, required, for instance, during the development of biosimilars. To the best of our knowledge, no evaluation of the efficacy of such a variety of compounds in the same cell culture system has been described. The studied cell culture media additives are efficient modulators of glycosylation and are thus a valuable tool to produce recombinant glycoproteins.
journal_name
Biotechnol Bioengjournal_title
Biotechnology and bioengineeringauthors
Ehret J,Zimmermann M,Eichhorn T,Zimmer Adoi
10.1002/bit.26904subject
Has Abstractpub_date
2019-04-01 00:00:00pages
816-830issue
4eissn
0006-3592issn
1097-0290journal_volume
116pub_type
杂志文章abstract::Addition of Tween 85 to aqueous suspensions of Anabaena variabilis induced photosynthetic evolution of hydrogen over a time span of several weeks: As much as 148 nmol H(2)/h . mg dry weight was produced in the first week by a suspension containing 4.2 mg dry weight of cells and 77 mM Tween 85. The chemical structure o...
journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260420812
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
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更新日期:2006-04-05 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260341105
更新日期:1989-12-20 00:00:00
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journal_title:Biotechnology and bioengineering
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更新日期:1998-11-05 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25538
更新日期:2015-07-01 00:00:00
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journal_title:Biotechnology and bioengineering
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doi:10.1002/bit.26386
更新日期:2017-11-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.25826
更新日期:2016-03-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/bit.260350309
更新日期:1990-02-05 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
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更新日期:2013-04-01 00:00:00
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
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更新日期:1985-08-01 00:00:00
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0290(19961005)52:1<141::AID-BIT
更新日期:1996-10-05 00:00:00
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
pub_type: 杂志文章
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journal_title:Biotechnology and bioengineering
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journal_title:Biotechnology and bioengineering
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