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J.C. Cruz, P.S. Bora, J. Sohn, Z. Hu, N.S. Bora, A. Garen, H.J. Kaplan; Immunotherapy of Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3934.
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Purpose: To explore immunotherapy with a mouse factor VII (MfVII) immunoconjugate (Icon) in a murine model of laser-induced choroidal neovascularization (CNV). MfVII Icon binds to tissue factor (TF) which is selectively expressed on CNV. Methods: CNV was induced by laser photocoagulation in the C57BL/6 mouse with the krypton red laser (0.05 sec., 100 uM, 250 mW). Three laser spots were placed in each eye. Mice (n=5, per group) were treated i.v. or intraocularly with adenovirus encoding MfVII adeno-Icon, purified Icon protein or human IgG (control protein). At the time of sacrifice mice were perfused with 1ml of 3% dextran(molecular weight 2 million Daltons).. Their eyes were enucleated, fixed (1h in10% phosphate buffered formalin) and RPE-choroidal-scleral flat mounts stained with an anti-elastin (Cy-3 conjugated) antibody. The incidence of CNV was determined by confocal microscopy. Results: The systemic injection of adeno-Icon shortly after the induction of CNV (on days 1 and 4) resulted in a decrease in the incidence of new vessel formation from 97% to 5%. A similar result was observed with injection of the adeno-Icon within the eye - either into the vitreous cavity or the subretinal space. When the systemic injection of the adeno-Icon was delayed until the CNV was well established (i.e. days 7 and 14) the incidence of new vessel formation was again reduced from 97% to5%. We also observed that the Icon protein alone was as effective as the adeno-Icon after both systemic or intraocular injection. Conclusions: We have identified a novel protocol for anti-angiogenesis therapy in a murine model of CNV. Immunotherapy with the mfVII Icon selectively destroys CNV through the targeting of NK cells and complement of the immune system. Since TF is selectively expressed in the CNV complex of exudative AMD, immunotherapy with mfVII Icon may be of benefit in humans.
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