| Autor: |
Ludwig DL; ImClone Systems Incorporated, 180 Varick Street, New York, NY 10014, USA. Dale.Ludwig@imclone.com, Witte L, Hicklin DJ, Prewett M, Bassi R, Burtrum D, Pereira DS, Jimenez X, Fox F, Saxena B, Zhou Q, Ma Y, Kang X, Patel D, Barry M, Kussie P, Zhu Z, Russell DA, Petersen WL, Jury TP, Gaitan-Gaitan F, Moran DL, Delannay X, Storrs BS, Tou J, Zupec ME, Gustafson KS, McIntyre J, Tarnowski SJ, Bohlen P |
| Jazyk: |
angličtina |
| Zdroj: |
Human antibodies [Hum Antibodies] 2004; Vol. 13 (3), pp. 81-90. |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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