Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment

被引:108
作者
Birchler, M
Viti, F
Zardi, L
Spiess, B
Neri, D
机构
[1] ETH Honggerberg, Inst Mol Biol & Biophys, CH-8093 Zurich, Switzerland
[2] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[3] Univ Zurich, Vet Chirurg Klin, ETH Zurich, Dept Appl Life Sci, CH-8057 Zurich, Switzerland
关键词
recombinant antibody; angiogenesis; photo dynamic therapy; fibronectin isoform; ED-B domain;
D O I
10.1038/13679
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:984 / 988
页数:5
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