title: Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed.
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.
authors.affiliation: ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. Dale.Ludwig@imclone.com
authors.forename: Dale L
authors.initials: DL
authors.lastname: Ludwig
authors.forename: Larry
authors.initials: L
authors.lastname: Witte
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hicklin
authors.forename: Marie
authors.initials: M
authors.lastname: Prewett
authors.forename: Rajiv
authors.initials: R
authors.lastname: Bassi
authors.forename: Douglas
authors.initials: D
authors.lastname: Burtrum
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pereira
authors.forename: Xenia
authors.initials: X
authors.lastname: Jimenez
authors.forename: Floyd
authors.initials: F
authors.lastname: Fox
authors.forename: Babita
authors.initials: B
authors.lastname: Saxena
authors.forename: Qinwei
authors.initials: Q
authors.lastname: Zhou
authors.forename: Yuemei
authors.initials: Y
authors.lastname: Ma
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Kang
authors.forename: Dipa
authors.initials: D
authors.lastname: Patel
authors.forename: Michael
authors.initials: M
authors.lastname: Barry
authors.forename: Paul
authors.initials: P
authors.lastname: Kussie
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Zhu
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Russell
authors.forename: William L
authors.initials: WL
authors.lastname: Petersen
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Jury
authors.forename: Fernando
authors.initials: F
authors.lastname: Gaitan-Gaitan
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Moran
authors.forename: Xavier
authors.initials: X
authors.lastname: Delannay
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Storrs
authors.forename: Jacob
authors.initials: J
authors.lastname: Tou
authors.forename: Mark E
authors.initials: ME
authors.lastname: Zupec
authors.forename: Karen S
authors.initials: KS
authors.lastname: Gustafson
authors.forename: John
authors.initials: J
authors.lastname: McIntyre
authors.forename: S Joseph
authors.initials: SJ
authors.lastname: Tarnowski
authors.forename: Peter
authors.initials: P
authors.lastname: Bohlen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D030821:Plants, Genetically Modified; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D014183:Transplantation, Heterologous; D003313:Zea mays / Q000235:genetics* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors; D000068818:Cetuximab