Evidence map›Paper›PMID 33675232›Full record

ArticleBiotechnology and bioengineering2021

A novel hydrogen peroxide evolved CHO host can improve the expression of difficult to express bispecific antibodies.

Rajesh K Mistry, Emma Kelsall, Si Nga Sou, Harriet Barker, Mike Jenns, Katie Willis, Fabio Zurlo, Diane Hatton, Suzanne J Gibson

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 30% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
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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

9 authors at 3 institutions in 2 countries.

Rajesh K MistryCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-9992-8735
Emma KelsallCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
Si Nga SouCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
Harriet BarkerCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
Mike JennsKymab Ltd, Cell Line Development, Biopharmaceutical Development, Kymab, Babraham Research Campus, Cambridge, UK.
Katie WillisDepartment of Life Sciences, Imperial College London, Berkshire, UK.
Fabio ZurloCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
Diane HattonCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.
Suzanne J GibsonCell Culture and Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-3228-9983
AstraZeneca (United Kingdom) · GBImperial College London · GBKymab (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The manufacture of bispecific antibodies by Chinese hamster ovary (CHO) cells is often hindered by lower product yields compared to monoclonal antibodies. Recently, reactive oxygen species have been shown to negatively impact antibody production. By contrast, strategies to boost cellular antioxidant capacity appear to be beneficial for recombinant protein expression. With this in mind, we generated a novel hydrogen peroxide evolved host using directed host cell evolution. Here we demonstrate that this host has heritable resistance to hydrogen peroxide over many generations, displays enhanced antioxidant capacity through the upregulation of several, diverse antioxidant defense genes such as those involved in glutathione synthesis and turnover, and has improved glutathione content. Additionally, we show that this host has significantly improved transfection recovery times, improved growth and viability properties in a fed-batch production process, and elevated expression of two industrially relevant difficult to express bispecific antibodies compared to unevolved CHO control host cells. These findings demonstrate that host cell evolution represents a powerful methodology for improving specific host cell characteristics that can positively impact the expression of difficult to express biotherapeutics.

Indexed as

CHO CellsHydrogen PeroxideAnimalsAntibodies, BispecificCricetulusOxidative StressRecombinant ProteinsTransfectionAntibodies, BispecificHydrogen PeroxideRecombinant Proteinsbispecific antibodyevolved hosthydrogen peroxideredox

Identifiers

PMID33675232
PMCPMC8252053
OpenAlexW3134615939

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.