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

Nat Biotechnol. 1999 Oct;17(10):984-8. doi: 10.1038/13679.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophages / genetics
  • Eye / blood supply*
  • Eye / metabolism
  • Humans
  • Immunoglobulin Fragments / genetics
  • Immunoglobulin Fragments / immunology*
  • Immunohistochemistry
  • Light Coagulation*
  • Neovascularization, Pathologic / radiotherapy*
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology

Substances

  • Immunoglobulin Fragments
  • Recombinant Proteins