Evidence map›Paper›PMID 30602334›Full record

ArticlemAbs2019

Modulating cell culture oxidative stress reduces protein glycation and acidic charge variant formation.

Stanley Chung, Jun Tian, Zhijun Tan, Jie Chen, Na Zhang, Yunping Huang, Erik Vandermark, Jongchan Lee, Michael Borys, Zheng Jian Li

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 39 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Stanley Chunga Department of Chemical Engineering , Northeastern University , Boston , MA.ORCID 0000-0003-3526-9731
Jun Tianb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.
Zhijun Tanb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.
Jie Chenb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.ORCID 0000-0001-7975-5817
Na Zhangb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.ORCID 0000-0002-1031-384X
Yunping Huangc Mass Spectrometry COE 1, Global Product Development and Supply , Bristol-Myers Squibb Company , Pennington , RJ.
Erik Vandermarkb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.
Jongchan Leeb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.
Michael Borysb Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.
Zheng Jian Lib Biologics Development, Global Product Development and Supply , Bristol-Myers Squibb Company , Devens , MA.ORCID 0000-0002-1941-4145
Bristol-Myers Squibb (United States) · USBristol-Myers Squibb (Germany) · DENortheastern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Controlling acidic charge variants is critical for an industrial bioprocess due to the potential impact on therapeutic efficacy and safety. Achieving a consistent charge variant profile at manufacturing scale remains challenging and may require substantial resources to investigate effective control strategies. This is partially due to incomplete understanding of the underlying causes for charge variant formation during the cell culture process. To address this gap, we examined the effects of four process input factors (temperature, iron concentration, feed media age, and antioxidant (rosmarinic acid) concentration) on charge variant profile. These factors were found to affect the charge profile by modulating the cell culture oxidative state. Process conditions with higher acidic peaks corresponded to elevated supernatant peroxide concentration, intracellular reactive oxygen species (ROS) levels, or both. Changes in glycation level were the primary cause of the charge heterogeneity, and for the first time, supernatant peroxide was found to positively correlate with glycation levels. Based on these findings, a novel mathematical model was developed to demonstrate that the rate of acidic species formation was exponentially proportional to the concentrations of supernatant peroxide and protein product. This work provides critical insights into charge variant formation during the cell culture process and highlights the importance of modulating of cell culture oxidative stress for charge variant control.

Indexed as

Models, TheoreticalAnimalsAntibodies, MonoclonalBioreactorsCell Culture TechniquesCHO CellsCricetinaeCricetulusOxidative StressAntibodies, MonoclonalantioxidantsBioprocessingcharge variantsmonoclonal antibodyoxidative stressreactive oxygen species (ROS)

Identifiers

PMID30602334
PMCPMC6343810
OpenAlexW2907699905

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.