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Tumor‐targeting properties of antibody–vascular endothelial growth factor fusion proteins
Author(s) -
Halin Cornelia,
Niesner Uwe,
Villani Maria Elena,
Zardi Luciano,
Neri Dario
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10674
Subject(s) - biodistribution , antibody , vascular endothelial growth factor , angiogenesis , fusion protein , cancer research , vascular permeability , kinase insert domain receptor , microbiology and biotechnology , chemistry , vascular endothelial growth factor a , pathology , immunology , biology , medicine , vegf receptors , biochemistry , gene , in vitro , recombinant dna
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 μg/mouse). © 2002 Wiley‐Liss, Inc.