INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED RECEPTOR ACTIVATION WITH ANTI-KINASE INSERT DOMAIN-CONTAINING RECEPTOR SINGLE-CHAIN ANTIBODIES FROM A PHAGE DISPLAY LIBRARY

Citation
Zp. Zhu et al., INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR-INDUCED RECEPTOR ACTIVATION WITH ANTI-KINASE INSERT DOMAIN-CONTAINING RECEPTOR SINGLE-CHAIN ANTIBODIES FROM A PHAGE DISPLAY LIBRARY, Cancer research, 58(15), 1998, pp. 3209-3214
Citations number
39
Categorie Soggetti
Oncology
Journal title
ISSN journal
00085472
Volume
58
Issue
15
Year of publication
1998
Pages
3209 - 3214
Database
ISI
SICI code
0008-5472(1998)58:15<3209:IOVEGF>2.0.ZU;2-N
Abstract
A single-chain antibody phage display library was constructed from spl een cells of mice immunized with a soluble form of a human vascular en dothelial growth factor (VEGF) receptor, kinase insert domain-containi ng receptor (KDR). After two rounds of biopanning, >90% of the clones recovered were specifically reactive to KDR. Subsequent selection iden tified two clones that blocked VEGF binding to KDR. The clones were ex pressed in Escherichia coli and purified as soluble single-chain Fv (s cFv) antibodies. The affinities of the scFv for binding to KDR were de termined by BIAcore analysis (2.1 x 10(-9)-5.9 x 10(-9) M). One scFv, p1C11, was shown to inhibit VEGF-induced KDR phosphorylation and VEGF- stimulated DNA synthesis in human umbilical vein endothelial cells. Th ere is much experimental evidence to suggest that the VEGF/KDR/Flk-1 p athway plays an important role in tumor angiogenesis, a process that i s essential for tumor growth and metastasis. The antibodies discussed here, which block VEGF binding to KDR, have potential clinical applica tion in the treatment of cancer and other diseases where pathological angiogenesis is involved.