Transgenic goats producing an improved version of cetuximab in milk [preprint]
Authors
Laible, GötzCole, Sally
Brophy, Brigid
Maclean, Paul
How Chen, Li
Pollock, Dan P.
Cavacini, Lisa A.
Fournier, Nathalie
De Romeuf, Christophe
Masiello, Nicholas C.
Gavin, William G.
Wells, David N.
Meade, Harry M.
UMass Chan Affiliations
MassBiologicsDocument Type
PreprintPublication Date
2020-06-10Keywords
Transgenic goatscetuximab
milk
therapeutic monoclonal antibodies
mAbs
Amino Acids, Peptides, and Proteins
Immunoprophylaxis and Therapy
Immunotherapy
Molecular Biology
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Show full item recordAbstract
Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for enhanced effectiveness and better safety profile compared to treatments with Erbitux. In addition, our study validates transgenic goats as an excellent platform for large-scale production of therapeutic mAbs.Source
bioRxiv 2020.06.05.137463; doi: https://doi.org/10.1101/2020.06.05.137463. Link to preprint on bioRxiv service.
DOI
10.1101/2020.06.05.137463Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29483Rights
The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/2020.06.05.137463
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC-BY-NC-ND 4.0 International license.