A fully human recombinant IgG-like bispecific antibody to both the epidermal growth factor receptor and the insulin-like growth factor receptor for enhanced antitumor activity.
|
| Abstract |
Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor receptor (IGFR) have been implicated in the tumorigenesis of a variety of cancers. Here we propose that simultaneous targeting of both receptors with a bispecific antibody would lead to enhanced antitumor activity. To this end, we produced a recombinant human IgG-like bispecific antibody, a Di-diabody, using the variable regions from two antagonistic antibodies: IMC-11F8 to EGFR and IMC-A12 to IGFR. The Di-diabody binds to both EGFR and IGFR and effectively blocked both EGF- and IGF-stimulated receptor activation and tumor cell proliferation. The Di-diabody also inherited the biological properties from both of its parent antibodies; it triggers rapid and significant IGFR internalization and degradation and mediates effective antibody-dependent cellular cytotoxicity in a variety of tumor cells. Finally, the Di-diabody strongly inhibited the growth of two different human tumor xenografts in vivo. Our results underscore the benefits of simultaneous targeting of two tumor targets with bispecific antibodies.
|
|---|---|
| Authors | Dan Lu, Haifan Zhang, Henry Koo, James Tonra, Paul Balderes, Marie Prewett, Eric Corcoran, Venkata Mangalampalli, Rajiv Bassi, Deborah Anselma, Dipa Patel, Xiaoqiang Kang, Dale L Ludwig, Daniel J Hicklin, Peter Bohlen, Larry Witte, Zhenping Zhu |
| Journal | The Journal of biological chemistry (J Biol Chem) Vol. 280 Issue 20 Pg. 19665-72 (May 20 2005) ISSN: 0021-9258 [Print] United States |
| PMID | 15757893 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!