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Transgenic goats producing an improved version of cetuximab in milk

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posted on 2023-05-03, 19:50 authored by Goetz LaibleGoetz Laible, Sally ColeSally Cole, Brigid BrophyBrigid Brophy, Paul MacleanPaul Maclean, Li How Chen, Dan Pollock, Lisa Cavacini, Nathalie Fournier, Christophe De Romeuf, Nicholas Masiello, William Gavin, David WellsDavid Wells, Harry Meade
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 10 g/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.

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Rights statement

© 2020 The Authors. FASEB BioAdvances published by the Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Language

  • English

Does this contain Māori information or data?

  • No

Publisher

Wiley

Journal title

FASEB BioAdvances

ISSN

2573-9832

Citation

Laible, G., Cole, S., Brophy, B., Maclean, P., Chen, L. H., Pollock, D. P., … Meade, H. M. (2020). Transgenic goats producing an improved version of cetuximab in milk. FASEB BioAdvances, 2(11), 638–652. doi:10.1096/fba.2020-00059

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