Evaluation of novel antimouse VEGFR2 antibodies as potential antiangiogenic or vascular targeting agents for tumor therapy

Sophia Ran, Xianming Huang, Amber Downes, Philip E. Thorpe

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We generated a panel of eight rat IgG2a monoclonal antibodies with high affinity for mouse VEGFR2 (KDR/ Flk-1), the main receptor that mediates the angiogenic effect of VEGF-A. The antibodies (termed RAFL, Rat Anti Flk) bound to dividing endothelial cells more strongly than they did to nondividing cells. Most of the RAFL antibodies blocked [125I]VEGF165 binding to VEGFR2. Three of eight antibodies localized to VEGFR2-positive tumor endothelium after intravenous injection into mice bearing orthotopic MDA-MB-231 breast carcinomas, as judged by indirect immunohistochemistry. An average of 60% of vessels in the tumors was stained. The majority (50-80%) of vessels were also stained in a variety of other human and murine tumors growing in mice. The antibodies did not bind detectably to the vascular endothelium in normal heart, lung, liver, and brain cortex, whereas the vascular endothelium in kidney glomerulus and pancreatic islets was stained. Treatment of mice bearing orthotopic MDA-MB-231 tumors with RAFL-1 antibody inhibited tumor growth by an average of 48% and reduced vascular density by 65%, compared to tumors in mice treated with control IgG. Vascular damage was not observed in normal organs, including kidneys and pancreas. These studies demonstrate that anti-VEGFR2 antibodies have potential for vascular targeting and imaging of tumors in vivo.

Original languageEnglish (US)
Pages (from-to)297-307
Number of pages11
JournalNeoplasia
Volume5
Issue number4
StatePublished - Jul 2003

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Blood Vessels
Antibodies
Neoplasms
Vascular Endothelium
Therapeutics
Kidney Glomerulus
Neoplasm Antibodies
Islets of Langerhans
Intravenous Injections
Vascular Endothelial Growth Factor A
Endothelium
Pancreas
Anti-Idiotypic Antibodies
Endothelial Cells
Immunoglobulin G
Immunohistochemistry
Monoclonal Antibodies
Breast Neoplasms
Kidney
Lung

Keywords

  • Angiogenesis
  • Flk-1
  • Inhibition
  • Monoclonal antibodies
  • VEGFR2

ASJC Scopus subject areas

  • Cancer Research

Cite this

Evaluation of novel antimouse VEGFR2 antibodies as potential antiangiogenic or vascular targeting agents for tumor therapy. / Ran, Sophia; Huang, Xianming; Downes, Amber; Thorpe, Philip E.

In: Neoplasia, Vol. 5, No. 4, 07.2003, p. 297-307.

Research output: Contribution to journalArticle

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