Active drug targeting with immunoconjugates to choroidal neovascularization

Purpose. Active drug targeting with monoclonal antibody to neovascular vess els 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 intens e laser photocoagulation in a cynomolgus monkey and to evaluate the in vitr o effect of immunoconjugates on endothelial cells. Methods. CNV membranes were surgically excised from 10 patients with AMD. E xperimental CNV was induced by intense laser photocoagulation in a cynomolg us monkey. Immunolocalization of CD105 on frozen sections of CNV lesions wa s studied by immunohistochemical evaluation. Anti-von Willebrand's factor a ntibody was used as an endothelial cell marker. The cytotoxic effect of imm unoconjugates of anti-CD105 monoclonal antibody and dextran binding mitomyc in C on human umbilical vein endothelial cells (HUVECs) was evaluated in vi tro. Results. Endothelial cells demonstrated strong immunoreactivity of CD105 in all surgically excised CNV membranes. In the monkey eye, CD105-positive ce lls were detected only in CNV lesions but not in normal chorioretinal tissu es. Immunoconjugates with anti-CD105 monoclonal antibody showed a specific inhibitory effect on proliferating HUVECs. Conclusions. These results suggest that anti-CD105 monoclonal antibody-medi ated drug targeting has a potential to treat CNV in AMD.