Stable Expression of Adalimumab in Nicotiana tabacum
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Production of monoclonal antibodies and pharmaceutical proteins in transgenic plants has been the focus of many research efforts for close to 30 years. Use of plants as bioreactors reduces large-scale production costs and minimizes risk for human pathogens contamination. Stable nuclear transformation of the plant genome offers a clear advantage in agricultural protein production platforms, limited only by the number of hectares that can be cultivated. We report here, for the first time, successful and stable expression of adalimumab in transgenic Nicotiana tabacum plants. The plant-derived adalimumab proved fully active and was shown to rescue L929 cells from the in vitro lethal effect of rhTNFα just as effectively as commercially available CHO-derived adalimumab (Humira). These results indicate that agricultural biopharming is an efficient alternative to mammalian cell-based expression platforms for the large-scale production of recombinant antibodies.
KeywordsPlant-derived antibody Plant-made pharmaceuticals Adalimumab Humira TNF-α Nicotiana tabacum
We thank Dr. Meirav Blanka for her help in the development of the quantitative ELISA and Dr. Yehudit Posen for critically reviewing this manuscript. This study was supported by the Minerva Center for bio-hybrid complex system.
- 13.Yusibov, V., Kushnir, N., & Streatfield, S. J. (2016). Antibody production in plants and green algae. Annual Review of Plant Biology, 67, 669–701. https://doi.org/10.1146/annurev-arplant-043015-111812.CrossRefGoogle Scholar
- 20.Decker, T., & Gifford, G. E. (1987). Cell-associated tumor necrosis factor (TNF) as a killing mechanism of activated cytotoxic Information about subscribing to The Journal of Immunology is online at: Mechanism of activated cytotoxic macrophages. Journal of Immunology, 138, 957–962.Google Scholar
- 21.Mitoma, H., Horiuchi, T., Tsukamoto, H., et al. (2008). Mechanisms for cytotoxic effects of anti-tumor necrosis factor agents on transmembrane tumor necrosis factor α-expressing cells: Comparison among infliximab, etanercept, and adalimumab. Arthritis and Rheumatism, 58, 1248–1257. https://doi.org/10.1002/art.23447.CrossRefGoogle Scholar
- 23.Committee for Proprietary Medicinal Products. (2004). Humira—European public assessment reports. Scientific discussion (pp. 1–25).Google Scholar
- 33.Ausubel, F. M., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A., et al. (1987). Protocols in molecular biology. New York, NY: Greene Publishing Associates and Wiley-Interscience John Wiley and Sons.Google Scholar