The use of catechins in Chinese hamster ovary cell media for the improvement of monoclonal antibody yields and a reduction of acidic species

Toronjo‐Urquiza, Luis; Acosta‐Martin, Adelina E.; James, David C.; Nagy, Tibor; Falconer, Robert J.

doi:10.1002/btpr.2980

Cited by 11 publications

(19 citation statements)

References 34 publications

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“…Similar dependencies of effector levels on CHO growth were observed for catechins trapping cells in Sphase [48]. By analogy, treatment of cells with AMP is concentration-dependent and resulted in S-phase accumulation.…”

Section: Discussionsupporting

confidence: 65%

Methylthioadenosine (MTA) boosts cell‐specific productivities of Chinese hamster ovary cultures: dosage effects on proliferation, cell cycle and gene expression

Verhagen

Zieringer

2020

FEBS Open Bio

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Section: Discussionsupporting

confidence: 65%

Methylthioadenosine (MTA) boosts cell‐specific productivities of Chinese hamster ovary cultures: dosage effects on proliferation, cell cycle and gene expression

Verhagen

Zieringer

2020

FEBS Open Bio

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“…The use of antioxidants in CHO cell cultures to improve monoclonal antibody production has been a topic of great interest [8,[33][34][35][36][37][38][39]. Nevertheless, the precise mechanisms by which RA impacts CHO cell growth, metabolism, and productivity need further elucidation.…”

Section: Discussionmentioning

confidence: 99%

Insights into the Impact of Rosmarinic Acid on CHO Cell Culture Improvement through Transcriptomics Analysis

Huang

Tian

et al. 2022

Processes

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The use of antioxidants in Chinese hamster ovary (CHO) cell cultures to improve monoclonal antibody production has been a topic of great interest. Nevertheless, the antioxidants do not have consistent benefits of production improvement, which might be cell line specific and/or process specific. In this work, we investigated how treatment with the antioxidant rosmarinic acid (RA) improved cell growth and titer in CHO cell cultures using transcriptomics. In particular, transcriptomics analysis indicated that RA treatment modified gene expression and strongly affected the MAPK and PI3K/Akt signaling pathways, which regulate cell survival and cell death. Moreover, it was observed that these signaling pathways, which had been identified to be up-regulated on day 2 and day 6 by RA, were also up-regulated over time (from initial growth phase day 2 to slow growth or protein production phase day 6) in both conditions. In summary, this transcriptomics analysis provides insights into the role of the antioxidant RA in industrial cell culture processes. The current study also represents an example in the industry of how omics can be applied to gain an in-depth understanding of CHO cell biology and to identify critical pathways that can contribute to cell culture process improvement and cell line engineering.

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“…Secreted recombinant proteins were quantified by ELISA. Cell concentrations were determined by direct cell counting with a Countess II FL counter to allow calculation of specific productivity, expressed as pg/cell/day, according to the following equation [30] :…”

Section: Evaluation Of Specific Productivitymentioning

confidence: 99%

“…Recombinant protein productivity is correlated to VCD and q p . [11,30] Here, we tested the cell cycle distribution of CHO cells using rylation is required for cells to exit G0 efficiently. [31] Via RT-qPCR (Figure 4E), it was found that the mRNA expression of CDK3 and Cyclin C decreased in CHO cells treated with apilimod.…”

Section: Effect Of Apilimod On Cell Cyclementioning

confidence: 99%

Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy

Xiao

Feng

et al. 2022

Biotechnology Journal

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Chinese hamster ovary (CHO) cells are expected to acquire the ability to produce higher recombinant therapeutic protein levels using various strategies. Genetic engineering targeting the cell cycle and autophagy pathways in the regulation of cell death in CHO cell cultures has received attention for enhancing the production of therapeutic proteins. In this study, we examined the small-molecule compound apilimod, which was found to have a positive influence on recombinant protein expression in CHO cells. This was confirmed by selective blocking of the cell cycle at the G0/G1 phase. Apilimod treatment resulted in decreased expression of cyclin-dependent kinase 3 (CDK3) and Cyclin C and increased expression of cyclin-dependent kinase suppressor p27Kip1, which are critical regulators of G1 cell cycle progression and important targets controlling cell proliferation. Furthermore, total transcription factor EB (TFEB) was lower in apilimod-treated CHO cells than in control cells, resulting in decreased lysosome biogenesis and autophagy with apilimod treatment. These multiple effects demonstrate the potential of apilimod for development as a novel enhancer for the production of recombinant proteins in CHO cell engineering.

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The use of catechins in Chinese hamster ovary cell media for the improvement of monoclonal antibody yields and a reduction of acidic species

Cited by 11 publications

References 34 publications

Methylthioadenosine (MTA) boosts cell‐specific productivities of Chinese hamster ovary cultures: dosage effects on proliferation, cell cycle and gene expression

Methylthioadenosine (MTA) boosts cell‐specific productivities of Chinese hamster ovary cultures: dosage effects on proliferation, cell cycle and gene expression

Insights into the Impact of Rosmarinic Acid on CHO Cell Culture Improvement through Transcriptomics Analysis

Apilimod enhances specific productivity in recombinant CHO cells through cell cycle arrest and mediation of autophagy

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