Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed |
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Authors: | Ludwig Dale L Witte Larry Hicklin Daniel J Prewett Marie Bassi Rajiv Burtrum Douglas Pereira Daniel S Jimenez Xenia Fox Floyd Saxena Babita Zhou Qinwei Ma Yuemei Kang Xiaoqiang Patel Dipa Barry Michael Kussie Paul Zhu Zhenping Russell Douglas A Petersen William L Jury Thomas P Gaitan-Gaitan Fernando Moran Daniel L Delannay Xavier Storrs Bradley S Tou Jacob Zupec Mark E Gustafson Karen S McIntyre John Tarnowski S Joseph Bohlen Peter |
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Institution: | ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. Dale.Ludwig@imclone.com |
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Abstract: | Recombinant protein production in plants such as corn is a promising means to generate high product yields at low comparable production cost. The anti-EGFR monoclonal antibody C225, cetuximab, is a well-characterized receptor antagonist antibody recently approved for the treatment of refractory colorectal cancer. We initiated a study to test and compare the functional activity of glycosylated and aglycosylated C225 produced in stable transgenic corn seed. Both corn antibodies were shown to be functionally indistinguishable from mammalian-derived C225 in demonstrating high-affinity binding to the EGF receptor, blocking of ligand-dependent signaling, and inhibiting cell proliferation. In addition, consistent with cetuximab, both corn antibodies possessed strong anti-tumor activity in vivo. Acute dose primate pharmacokinetic studies, however, revealed a marked increase in clearance for the glycosylated corn antibody, while the aglycosylated antibody possessed in vivo kinetics similar to cetuximab. This experimentation established that corn-derived receptor blocking monoclonal antibodies possess comparable efficacy to mammalian cell culture-derived antibody, and offer a cost effective alternative to large-scale mammalian cell culture production. |
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