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Active drug targeting with immunoconjugates to choroidal neovascularization
T Yasukawa1, H Kimura, Y Tabata
1Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
Current Eye Research
|March 23, 2001
Summary
Targeting endoglin (CD105) with monoclonal antibodies shows promise for treating choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This approach specifically inhibits proliferating endothelial cells in CNV lesions.
Area of Science:
- Ophthalmology
- Oncology
- Vascular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss in age-related macular degeneration (AMD).
- Active drug targeting of neovascular vessels offers a potential therapeutic strategy for CNV.
- Endoglin (CD105) is a marker of proliferating endothelial cells, making it a promising target.
Purpose of the Study:
- To investigate CD105 expression in human AMD CNV membranes and experimentally induced CNV in cynomolgus monkeys.
- To evaluate the in vitro efficacy of anti-CD105 immunoconjugates on endothelial cells.
Main Methods:
- Surgical excision of CNV membranes from 10 AMD patients.
- Induction of experimental CNV in cynomolgus monkeys via laser photocoagulation.
- Immunohistochemical localization of CD105 and evaluation of anti-CD105 immunoconjugate cytotoxicity on human umbilical vein endothelial cells (HUVECs) in vitro.
Main Results:
- Strong CD105 immunoreactivity was observed in endothelial cells of human CNV membranes.
- CD105-positive cells were exclusively found in laser-induced CNV lesions in monkey eyes, not in normal tissues.
- Anti-CD105 immunoconjugates demonstrated specific inhibition of proliferating HUVECs in vitro.
Conclusions:
- The findings suggest that targeting CD105 with monoclonal antibodies is a viable strategy for treating CNV in AMD.
- Anti-CD105 monoclonal antibody-mediated drug targeting holds potential for therapeutic intervention in CNV.