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