Conservation of receptor antagonist anti-tumor activity by epidermal growth factor receptor antibody expressed in transgenic corn seed.
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.
Ludwig
Dale L
DL
ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. Dale.Ludwig@imclone.com
Witte
Larry
L
Hicklin
Daniel J
DJ
Prewett
Marie
M
Bassi
Rajiv
R
Burtrum
Douglas
D
Pereira
Daniel S
DS
Jimenez
Xenia
X
Fox
Floyd
F
Saxena
Babita
B
Zhou
Qinwei
Q
Ma
Yuemei
Y
Kang
Xiaoqiang
X
Patel
Dipa
D
Barry
Michael
M
Kussie
Paul
P
Zhu
Zhenping
Z
Russell
Douglas A
DA
Petersen
William L
WL
Jury
Thomas P
TP
Gaitan-Gaitan
Fernando
F
Moran
Daniel L
DL
Delannay
Xavier
X
Storrs
Bradley S
BS
Tou
Jacob
J
Zupec
Mark E
ME
Gustafson
Karen S
KS
McIntyre
John
J
Tarnowski
S Joseph
SJ
Bohlen
Peter
P
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*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D066246:ErbB Receptors; D000068818:Cetuximab