Inhibition of tumor angiogenesis by a single-chain antibody directed against vascular endothelial growth factor.
Monoclonal antibody (Ab) directed against the vascular endothelial growth factor, one of the major inducers of angiogenesis, can inhibit tumor growth in mice. Treatment of cancer patients with monoclonal Ab requires large-scale production of the clean Ab and frequent application of the Ab. This might be improved by using single-chain Ab fragments (scFvs), which can be produced in large quantities in bacteria and are attractive for gene therapeutic approaches. Here we describe anti-vascular endothelial growth factor scFvs derived from a human phage-display library able to block the vascularization of the chorioallantoic membrane of chick embryos and reduce the growth of s.c. tumors in nude mice. This work opens the way to develop gene therapy-based strategies using a scFv to treat angiogenesis-dependent diseases.
Vitaliti
A
A
Department of Pathology, University Hospital, Zurich, Switzerland.
Wittmer
M
M
Steiner
R
R
Wyder
L
L
Neri
D
D
Klemenz
R
R
D016475:3T3 Cells; D000482:Allantois / Q000098:blood supply; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D002461:Cell Line, Transformed; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D016228:Endothelial Growth Factors / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D008222:Lymphokines / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019151:Peptide Library; D051381:Rats; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D016228:Endothelial Growth Factors; D007128:Immunoglobulin Fragments; D008222:Lymphokines; D019151:Peptide Library; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors