Birchler M, Viti F, Zardi L, Spiess B, Neri D
Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg, Einsteinstrasse, CH-8093 Zürich, Switzerland.
Nat Biotechnol. 1999 Oct;17(10):984-8. doi: 10.1038/13679.
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.
能够选择性靶向并封闭新生血管的分子，将有助于诊断和治疗与血管生成相关的病症。我们发现，一种源自噬菌体的人抗体片段（L19）对纤连蛋白的ED-B结构域（血管生成的标志物）具有高亲和力，在兔眼血管生成模型中，它能选择性地定位于新生血管。将L19抗体与一种光敏剂化学偶联，并用红光照射，可介导眼新生血管的完全性和选择性封闭，并促进相应内皮细胞的凋亡。这些结果表明，新生眼血管可通过免疫化学方法与既有血管区分开来，提示光敏剂的靶向递送可能有效治疗血管生成相关病症。
