Literature DB >> 35608667

Recombinant antibodies aggregation and overcoming strategies in CHO cells.

Tingting Xu1,2, Jihong Zhang1,3, Tianyun Wang4,5, Xiaoyin Wang6,7.   

Abstract

Mammalian cell lines are frequently used as the preferred host cells for producing recombinant therapeutic proteins (RTPs) having post-translational modified modifications similar to those observed in proteins produced by human cells. Nowadays, most RTPs approved for marketing are produced in Chinese hamster ovary (CHO) cells. Recombinant therapeutic antibodies (RTAs) are among the most important and promising RTPs for biomedical applications. A major limitation associated with the use of RTAs is their aggregation, which can be caused by a variety of factors; this results in a reduction of quality. RTA aggregations are especially concerning as they can trigger human immune responses in humans and may be fatal. Therefore, the mechanisms underlying RTA aggregation and measures for avoiding aggregation are interesting topics in RTAs research. In this review, we discuss recent progress in the field of RTAs aggregation, with a focus on factors that cause aggregation during RTA production and the development of strategies for overcoming RTA aggregation. KEY POINTS: • The recombinant antibody aggregation in mammalian cell systems is reviewed. • Intracellular environment and extracellular parameters influence recombinant antibody aggregation. • Reducing the aggregations can improve the quality of recombinant antibodies.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Entities:  

Keywords:  Aggregation; Bioprocess engineering; Chinese hamster ovary cells; Folding; Recombinant antibody

Mesh:

Substances:

Year:  2022        PMID: 35608667     DOI: 10.1007/s00253-022-11977-0

Source DB:  PubMed          Journal:  Appl Microbiol Biotechnol        ISSN: 0175-7598            Impact factor:   4.813


  83 in total

Review 1.  Protein aggregation and bioprocessing.

Authors:  Mary E M Cromwell; Eric Hilario; Fred Jacobson
Journal:  AAPS J       Date:  2006-09-15       Impact factor: 4.009

2.  Aggregation-prone motifs in human immunoglobulin G.

Authors:  Naresh Chennamsetty; Bernhard Helk; Vladimir Voynov; Veysel Kayser; Bernhardt L Trout
Journal:  J Mol Biol       Date:  2009-06-13       Impact factor: 5.469

Review 3.  The fickle CHO: a review of the causes, implications, and potential alleviation of the CHO cell line instability problem.

Authors:  Hussain Dahodwala; Kelvin H Lee
Journal:  Curr Opin Biotechnol       Date:  2019-02-28       Impact factor: 9.740

4.  Evaluation of different vector design strategies for the expression of recombinant monoclonal antibody in CHO cells.

Authors:  Hadi Bayat; Saghar Hossienzadeh; Eśhagh Pourmaleki; Roshanak Ahani; Azam Rahimpour
Journal:  Prep Biochem Biotechnol       Date:  2018-02-09       Impact factor: 2.162

5.  Effect of increased expression of protein disulfide isomerase and heavy chain binding protein on antibody secretion in a recombinant CHO cell line.

Authors:  Nicole Borth; Diethard Mattanovich; Renate Kunert; Hermann Katinger
Journal:  Biotechnol Prog       Date:  2005 Jan-Feb

6.  Autophagy and intracellular product degradation genes identified by systems biology analysis reduce aggregation of bispecific antibody in CHO cells.

Authors:  Mona Moradi Barzadd; Magnus Lundqvist; Claire Harris; Magdalena Malm; Anna-Luisa Volk; Niklas Thalén; Veronique Chotteau; Luigi Grassi; Andrew Smith; Marina Leal Abadi; Giulia Lambiase; Suzanne Gibson; Diane Hatton; Johan Rockberg
Journal:  N Biotechnol       Date:  2022-02-02       Impact factor: 5.079

7.  Reversible NaCl-induced aggregation of a monoclonal antibody at low pH: Characterization of aggregates and factors affecting aggregation.

Authors:  Fabian Bickel; Eva Maria Herold; Alba Signes; Stefan Romeijn; Wim Jiskoot; Hans Kiefer
Journal:  Eur J Pharm Biopharm       Date:  2016-07-20       Impact factor: 5.571

8.  Unique Impacts of Methionine Oxidation, Tryptophan Oxidation, and Asparagine Deamidation on Antibody Stability and Aggregation.

Authors:  Magfur E Alam; Thomas R Slaney; Lina Wu; Tapan K Das; Sambit Kar; Gregory V Barnett; Anthony Leone; Peter M Tessier
Journal:  J Pharm Sci       Date:  2019-10-31       Impact factor: 3.534

9.  Engineering a therapeutic IgG molecule to address cysteinylation, aggregation and enhance thermal stability and expression.

Authors:  Andrew Buchanan; Veronica Clementel; Rob Woods; Nicholas Harn; Michael A Bowen; Wenjun Mo; Bojana Popovic; Steven M Bishop; William Dall'Acqua; Ralph Minter; Lutz Jermutus; Vahe Bedian
Journal:  MAbs       Date:  2013-02-14       Impact factor: 5.857

Review 10.  The making of bispecific antibodies.

Authors:  Ulrich Brinkmann; Roland E Kontermann
Journal:  MAbs       Date:  2017 Feb/Mar       Impact factor: 5.857

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