Evidence map›Paper›PMID 38001891›Full record

ArticleBiomedicines2023

Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody.

Maria João Sebastião, Michael Hoffman, José Escandell, Fatemeh Tousi, Jin Zhang, Bruno Figueroa, Christine DeMaria, Patrícia Gomes-Alves

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

6 citing papers in PubMed, 7 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

8 authors at 1 institution in 1 country.

Maria João SebastiãoiBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.
Michael HoffmanSanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA.
José EscandelliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.ORCID 0000-0003-4857-9413
Fatemeh TousiSanofi Bioanalytics Development, Global CMC Development, Framingham, MA 01701, USA.
Jin ZhangSanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA.
Bruno FigueroaSanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA.
Christine DeMariaSanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA.
Patrícia Gomes-AlvesiBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2780-901 Oeiras, Portugal.ORCID 0000-0001-7245-6785
Instituto de Biologia Experimental e Tecnológica · PT

Funding

Fundação para a Ciência e Tecnologia LA/P/0087/2020Fundação para a Ciência e Tecnologia UIDB/04462/2020Fundação para a Ciência e Tecnologia UIDP/04462/2020
6 · The paper itself

Abstract

Monoclonal antibody-based therapy has shown efficacy against cancer, autoimmune, infectious, and inflammatory diseases. Multispecific antibodies (MsAbs), including trispecifics (tsAbs), offer enhanced therapeutic potential by targeting different epitopes. However, when co-expressed from three or more different polypeptide chains, MsAb production can lead to incorrect chain assembly and co-production of mispaired species with impaired biological activity. Moreover, mispairing carries significant challenges for downstream purification, decreasing yields and increasing the cost of bioprocess development. In this study, quantitative transcriptomics and proteomics analyses were employed to investigate which signaling pathways correlated with low and high mispairing clone signatures. Gene and protein expression profiles of Chinese hamster ovary (CHO) clones producing an tsAb were analyzed in the exponential growth and stationary (tsAb production) phase of fed-batch culture. Functional analysis revealed activated endoplasmic reticulum stress in high mispairing clones in both culture phases, while low mispairing clones exhibited expression profiles indicative of activated protein translation, as well as higher endocytosis and target protein degradation, suggesting the clearance of unfolded proteins through ubiquitin-mediated mechanisms. In addition, through transcriptomic profiling, we identified a group of genes that have the potential to be used as a biomarker panel tool for identifying high mispairing levels in the early stages of bioprocess development.

Indexed as

CHO cellsmispairingmultispecific antibodiesproteomicstranscriptomics

Identifiers

PMID38001891
PMCPMC10669571
OpenAlexW4387935779

What OpenQuestion holds

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LicenceCC BY
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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.