Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.
Bora
Puran S
PS
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40202, USA.
Hu
Zhiwei
Z
Tezel
Tongalp H
TH
Sohn
Jeong-Hyeon
JH
Kang
Shin Goo
SG
Cruz
Jose M C
JM
Bora
Nalini S
NS
Garen
Alan
A
Kaplan
Henry J
HJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects*; D018076:DNA, Complementary / Q000378:metabolism; D004195:Disease Models, Animal; D015723:Gene Library; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007834:Lasers; D008099:Liver / Q000378:metabolism; D008268:Macular Degeneration / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic; D011485:Protein Binding; D012160:Retina / Q000187:drug effects; D013552:Swine; D013925:Thromboplastin / Q000378:metabolism
D018076:DNA, Complementary; D013925:Thromboplastin