Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed

Article type: Research Article

Authors: Ludwig, Dale L.^{a; *} | Witte, Larry^a | Hicklin, Daniel J.^a | Prewett, Marie^a | Bassi, Rajiv^a | Burtrum, Douglas^a | Pereira, Daniel S.^a | Jimenez, Xenia^a | Fox, Floyd^b | Saxena, Babita^b | Zhou, Qinwei^b | Ma, Yuemei^b | Kang, Xiaoqiang^a | Patel, Dipa^a | Barry, Michael^b | Kussie, Paul^a | Zhu, Zhenping^a | Russell, Douglas A.^{c; **} | Petersen, William L.^c | Jury, Thomas P.^c | Gaitan-Gaitan, Fernando^c | Moran, Daniel L.^c | Delannay, Xavier^c | Storrs, Bradley S.^c | Tou, Jacob^c | Zupec, Mark E.^c | Gustafson, Karen S.^c | McIntyre, John^c | Tarnowski, S. Joseph^b | Bohlen, Peter^a

Affiliations: [a] ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA | [b] ImClone Systems Incorporated, 22 Chubb Way, Somerville, NJ 08876, USA | [c] Monsanto Protein Technologies, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA

Correspondence: [*] Corresponding author: Dr. Dale L. Ludwig, Department of Molecular Biology, ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. Tel.: +1 646 638 5187; Fax: +1 212 645 2054; E-mail: [email protected].

Note: [**] Current address: Syngenta, Jealotts Hill Research Centre, Bracknell rg42 6ey, UK.

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. Erratum: 10.3233/HAB-2009-0208.

Keywords: antibodies, transgenic plants, epidermal growth factor receptor, cancer

DOI: 10.3233/HAB-2004-13304

Journal: Human Antibodies, vol. 13, no. 3, pp. 81-90, 2004