Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment.
Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.
Birchler
M
M
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, Einsteinstrasse, CH-8093 Zürich, Switzerland.
Viti
F
F
Zardi
L
L
Spiess
B
B
Neri
D
D
D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D005123:Eye / Q000098:blood supply* / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology*; D007150:Immunohistochemistry; D008028:Light Coagulation; D009389:Neovascularization, Pathologic / Q000532:radiotherapy*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins