Active drug targeting with immunoconjugates to choroidal neovascularization.
OBJECTIVE
Active drug targeting with monoclonal antibody to neovascular vessels may be a potential treatment for choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Endoglin (CD105) is a proliferating endothelial cell marker with excellent potential for targeting. The goals of this study were to investigate the expression of CD105 in CNV membranes surgically excised from patients with AMD and CNV lesions induced by intense laser photocoagulation in a cynomolgus monkey and to evaluate the in vitro effect of immunoconjugates on endothelial cells.


METHODS
CNV membranes were surgically excised from 10 patients with AMD. Experimental CNV was induced by intense laser photocoagulation in a cynomolgus monkey. Immunolocalization of CD105 on frozen sections of CNV lesions was studied by immunohistochemical evaluation. Anti-von Willebrand's factor antibody was used as an endothelial cell marker. The cytotoxic effect of immunoconjugates of anti-CD105 monoclonal antibody and dextran binding mitomycin C on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro.


RESULTS
Endothelial cells demonstrated strong immunoreactivity of CD105 in all surgically excised CNV membranes. In the monkey eye, CD105-positive cells were detected only in CNV lesions but not in normal chorioretinal tissues. Immunoconjugates with anti-CD105 monoclonal antibody showed a specific inhibitory effect on proliferating HU-VECs.


CONCLUSIONS
These results suggest that anti-CD105 monoclonal antibody-mediated drug targeting has a potential to treat CNV in AMD.
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
T
T
Yasukawa
H
H
Kimura
Y
Y
Tabata
H
H
Miyamoto
Y
Y
Honda
Y
Y
Ikada
Y
Y
Ogura
D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003911:Dextrans / Q000494:pharmacology*; D016503:Drug Delivery Systems; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D018796:Immunoconjugates; D007124:Immunoenzyme Techniques; D017075:Laser Coagulation / Q000009:adverse effects; D008252:Macaca fascicularis; D008268:Macular Degeneration / Q000150:complications; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D003911:Dextrans; C064206:ENG protein, human; D000071063:Endoglin; D018796:Immunoconjugates; D011355:Prodrugs; D011956:Receptors, Cell Surface; D019010:Vascular Cell Adhesion Molecule-1; C042790:mitomycin C-dextran; D016685:Mitomycin