ArticleScientific reports2020
Perfusion reduces bispecific antibody aggregation via mitigating mitochondrial dysfunction-induced glutathione oxidation and ER stress in CHO cells.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- DTT-Induced Transcriptome Profiling Reveals Divergent ER Proteostasis and Stress-Adaptation Programs in CHO-S/HB8 and CHO-4BGD/DUL Producer Clones.International journal of molecular sciences · 2026Article
- Leveraging ANXA1 to enhance recombinant protein yields in CHO cells: A UPR-Mediated bioprocessing approach.Synthetic and systems biotechnology · 2026Article
- Challenges and solutions for upstream processing of complex biologics.Antibody therapeutics · 2026Review
- Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines.International journal of molecular sciences · 2025Review
- From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems.International journal of molecular sciences · 2025Review
- Proteomics Reveals Distinctive Host Cell Protein Expression Patterns in Fed-Batch and Perfusion Cell Culture Processes.Biotechnology journal · 2025Article
- Engineering and physicochemical characterization of a novel, stable, symmetric bispecific antibody with dual target-binding using a common light chain.Protein science : a publication of the Protein Society · 2024Article
- Impact of fed-batch process intensification on the productivity and product quality of two CHO cell lines expressing unique novel molecular format proteins.Bioprocess and biosystems engineering · 2024Article
- Decoupling Protein Concentration and Aggregate Content Using Diffusion and Water NMR.Analytical chemistry · 2024Article
- RNASeq highlights ATF6 pathway regulators for CHO cell engineering with different impacts of ATF6β and WFS1 knockdown on fed-batch production of IgGScientific reports · 2024Article
- A miniaturized culture platform for control of the metabolic environment.Biomicrofluidics · 2024Article
- Dissecting cell death pathways in fed-batch bioreactors.Biotechnology journal · 2024Article
- Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody.Biomedicines · 2023Article
- WAVE-based intensified perfusion cell culture for fast process development.Biotechnology letters · 2023Article
- Recombinant antibodies aggregation and overcoming strategies in CHO cells.Applied microbiology and biotechnology · 2022Review
- Productivity and quality improvement for a symmetric bispecific antibody through the application of intensified perfusion cell culture.Antibody therapeutics · 2022Article
- CDMOs Play a Critical Role in the Biopharmaceutical Ecosystem.Frontiers in bioengineering and biotechnology · 2022Review
- Enhancing CHO cell recombinant protein production using a perfusion-directed host evolution approach.Biotechnology progressArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One major challenge observed for the expression of therapeutic bispecific antibodies (BisAbs) is high product aggregates. Aggregates increase the risk of immune responses in patients and therefore must be removed at the expense of purification yields. BisAbs contain engineered disulfide bonds, which have been demonstrated to form product aggregates, if mispaired. However, the underlying intracellular mechanisms leading to product aggregate formation remain unknown. We demonstrate that impaired glutathione regulation underlies BisAb aggregation formation in a CHO cell process. Aggregate formation was evaluated for the same clonal CHO cell line producing a BisAb using fed-batch and perfusion processes. The perfusion process produced significantly lower BisAb aggregates compared to the fed-batch process. Perfusion bioreactors attenuated mitochondrial dysfunction and ER stress resulting in a favorable intracellular redox environment as indicated by improved reduced to oxidized glutathione ratio. Conversely, mitochondrial dysfunction-induced glutathione oxidation and ER stress disrupted the intracellular redox homeostasis, leading to product aggregation in the fed-batch process. Combined, our results demonstrate that mitochondrial dysfunction and ER stress impaired glutathione regulation leading to higher product aggregates in the fed-batch process. This is the first study to utilize perfusion bioreactors as a tool to demonstrate the intracellular mechanisms underlying product aggregation formation.
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Registered trials
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.