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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-10-17
pubmed:abstractText
A major problem of antibody-based targeting of solid tumors is the poor penetration of antibodies into tumor tissue. Vasoactive immunoconjugates have been proposed as a means of increasing antibody uptake in tumors. In principle, VEGF (also known as vascular permeability factor) could selectively alter vascular permeability, leading to improved tumor targeting. A possible role for VEGF in the targeting of tumor neovasculature has been postulated, based on the overexpression of VEGF receptors in tumor endothelial cells. However, quantitative biodistribution studies on this topic are not available. In this report, we describe the cloning, expression, characterization and biodistribution in tumor-bearing mice of antibodies fused to either VEGF(120) or VEGF(164) The MAb fragments chosen for analysis were scFv(L19), specific for the ED-B domain of fibronectin, a marker of angiogenesis, and scFv(HyHEL-10), a negative control antibody of irrelevant specificity in mice. Neither unconjugated VEGF nor scFv(HyHEL-10)-VEGF fusion proteins showed accumulation in the tumor (tumor:blood ratios approx. 1 at 4 hr and 24 hr postinjection). By contrast, scFv(L19)-VEGF(120) but not scFv(L19)-VEGF(164) showed significant accumulation in tumors (tumor:blood ratio = 9.3 at 24 hr) but was not superior to unconjugated scFv(L19). Preinjection of unlabeled scFv(L19)-VEGF(120) prior to administration of radiolabeled fusion protein led to increased accumulation of radiolabeled scFv(L19)-VEGF(120) in the tumor but only at very high concentrations (20 microg/mouse).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-16
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Tumor-targeting properties of antibody-vascular endothelial growth factor fusion proteins.
pubmed:affiliation
Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology-Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't