in vitro and in vivo pharmacology and pharmacokinetics of a human engineered™ monoclonal antibody to epithelial cell adhesion molecule
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ID: 169256
2003
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Abstract
ING-1(heMAb), a Human Engineered™ monoclonal antibody to epithelial cell adhesion molecule (Ep-CAM ), was evaluated for its in vitro and in vivo activity. The dissociation constant of ING-1(heMAb) for binding to Ep-CAM on HT-29 human colon tumor cells was 2 to 5 nM, similar to chimeric ING-1. In antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity assays, ING-1(heMAb) caused a concentration-dependent lysis of BT-20 breast, MCF-7 breast, HT-29 colon, CACO-2 colon tumor cells, with maximum cytolysis at approximately 1 μg/ml. After an intravenous injection in rats, plasma ING-1(heMAb) levels declined with an alpha half-life of 8 to 11 hours, a beta half-life of 20 days, typical of an IgG in a species without the target for ING-1. In nude mice with human HT-29 colon tumors, plasma ING-1(heMAb) levels declined more rapidly than in non-tumor-bearing mice, suggesting an enhanced clearance via the tumor-associated human Ep-CAM. In nude mice, intravenous treatments with ING-1(heMAb) twice a week for 3 weeks significantly suppressed the growth of human HT-29 colon and PC-3 prostate tumors in a dose-dependent manner, with 1.0 mg/kg providing the greatest benefit. These results indicate that Human Engineered™ ING-1(heMAb) is a high-affinity antibody with potent in vitro activity that targets and suppresses the growth of human tumors in vivo.
| Reference Key |
ammons2003neoplasia:in
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|---|---|
| Authors | ;W. Steve Ammons;Robert J. Bauer;Arnold H. Horwitz;Zhi J. Chen;Eddie Bautista;Harry H. Ruan;Marina Abramova;Kristen R. Scott;Russell L. Dedrick |
| Journal | ACS chemical neuroscience |
| Year | 2003 |
| DOI |
10.1016/S1476-5586(03)80006-4
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| URL | |
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