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Inhibition of vascular endothelial growth factor induced mitogenesis of human endothelial cells by a chimeric anti-kinase insert domain-containing receptor antibody.

Abstract：

:The kinase insert domain-containing receptor (KDR) is the human vascular endothelial growth factor (VEGF) receptor responsible for the mitogenic and angiogenic effects of VEGF. There is much experimental evidence to suggest that the VEGF/KDR pathway plays an important role in tumor angiogenesis, a process essential for tumor growth and metastasis. Here we produced a chimeric anti-KDR antibody (IgG1), c-p1C11, from a single chain (scFv) antibody isolated from a phage display library. C-p1C11 binds specifically to the extracellular domain of soluble as well as cell-surface expressed KDR. It effectively blocks VEGF-KDR interaction and inhibits VEGF-stimulated activation of KDR and MAP kinases p44/p42 of human endothelial cells. Furthermore, c-p1C11 efficiently neutralizes VEGF-induced mitogenesis of human endothelial cells. Our results suggest that antibodies against KDR have potential clinical applications in the treatment of cancer and other diseases where pathological angiogenesis is involved.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Zhu Z,Lu D,Kotanides H,Santiago A,Jimenez X,Simcox T,Hicklin DJ,Bohlen P,Witte L

doi

10.1016/s0304-3835(98)00324-3

keywords:

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

203-13

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(98)00324-3

journal_volume

136

pub_type

杂志文章

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