Transgenic goats producing an improved version of cetuximab in milk

Laible, G.; Cole, S.; Brophy, B.; Maclean, P.; Chen, L. H.; Pollock, D. P.; Cavacini, L.; Fournier, N.; De Romeuf, C.; Masiello, N. C.; Gavin, W. G.; Wells, D. N.; Meade, H. M.

doi:10.1101/2020.06.05.137463

bioRxiv · 10.1101/2020.06.05.137463

Transgenic goats producing an improved version of cetuximab in milk

Laible, G.·Cole, S.·Brophy, B.·Maclean, P.·Chen, L. H.·Pollock, D. P.·Cavacini, L.·Fournier, N.·De Romeuf, C.·Masiello, N. C.·Gavin, W. G.·Wells, D. N.·Meade, H. M.

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Abstract

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.

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Laible, G., Cole, S., Brophy, B., Maclean, P., Chen, L. H., Pollock, D. P., Cavacini, L., Fournier, N., De Romeuf, C., Masiello, N. C., Gavin, W. G., Wells, D. N., Meade, H. M.. 2020-06-07. Transgenic goats producing an improved version of cetuximab in milk. https://doi.org/10.1101/2020.06.05.137463

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