A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor : receptor complex

Citation
Sp. Cooke et al., A strategy for antitumor vascular therapy by targeting the vascular endothelial growth factor : receptor complex, CANCER RES, 61(9), 2001, pp. 3653-3659
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
9
Year of publication
2001
Pages
3653 - 3659
Database
ISI
SICI code
0008-5472(20010501)61:9<3653:ASFAVT>2.0.ZU;2-J
Abstract
Vascular endothelial growth Factor (VEGF) is produced by cancer cells in re sponse to hypoxia and Is the primary stimulant of vascularization in solid tumors. Endothelial cells lining the blood vessels of these tumors have a h igh concentration of receptor-bound VEGF on their surface, providing a targ et for antibody- directed cancer therapy. To obtain a cloned antibody to ti lls target when bound to its receptor on tumor endothelium, we used phage d isplay technology to create a single-chain Fv (sFv) antibody library from m ice immunized with the 165-amino acid isoform of human VEGF-A. We selected, purified, and characterized LL4, an anti-VEGF sFv that was shown to react with receptor-hound VEGF. LL4 bound selectively to blood vessel endothelium , as shown by immunohistochemistry on tissue sections of human tumors. Furt hermore, using autoradiography and grain counting of histological sections, systemically administered LL4 was shown to localize selectively to the end othelial lining of tumor blood vessels in human colorectal carcinoma xenogr afts in vivo. This study demonstrates the feasibility of targeting tumor va sculature using recombinant antibodies to the VEGF:receptor complex.