A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice.
Songyi Seo, Koung Li Kim, Yeongju Yeo, Ryul-I Kim, Hayoung Jeong, Jin-Ock Kim, Sun-Hwa Song, Mi-Jin An, Jung-Woong Kim, Hye Kyoung Hong, Min Hee Ham, Se Joon Woo, Jong-Hyuk Sung, Sang Gyu Park, Wonhee Suh
Author Information
Songyi Seo: Department of Global Innovative Drug, Graduate School of Chung-Ang University, Seoul 06974, Korea.
Koung Li Kim: College of Pharmacy, Chung-Ang University, Seoul 06974, Korea.
Yeongju Yeo: Department of Global Innovative Drug, Graduate School of Chung-Ang University, Seoul 06974, Korea.
Ryul-I Kim: Department of Global Innovative Drug, Graduate School of Chung-Ang University, Seoul 06974, Korea.
Hayoung Jeong: Department of Global Innovative Drug, Graduate School of Chung-Ang University, Seoul 06974, Korea.
Jin-Ock Kim: College of Pharmacy, Ajou University, Suwon 16499, Korea.
Sun-Hwa Song: College of Pharmacy, Ajou University, Suwon 16499, Korea.
Mi-Jin An: Department of Life Science, Chung-Ang University, Seoul 06974, Korea. ORCID
Jung-Woong Kim: Department of Life Science, Chung-Ang University, Seoul 06974, Korea. ORCID
Hye Kyoung Hong: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Min Hee Ham: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Se Joon Woo: Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. ORCID
Jong-Hyuk Sung: College of Pharmacy, Yonsei University, Incheon 21983, Korea.
Sang Gyu Park: College of Pharmacy, Ajou University, Suwon 16499, Korea. ORCID
Wonhee Suh: Department of Global Innovative Drug, Graduate School of Chung-Ang University, Seoul 06974, Korea. ORCID
Stem cell factor (SCF) and its receptor, cKIT, are novel regulators of pathological neovascularization in the eye, which suggests that inhibition of SCF/cKIT signaling may be a novel pharmacological strategy for treating neovascular age-related macular degeneration (AMD). This study evaluated the therapeutic potential of a newly developed fully Human monoclonal antibody targeting cKIT, NN2101, in a murine model of neovascular AMD. In hypoxicHuman endothelial cells, NN2101 substantially inhibited the SCF-induced increase in angiogenesis and activation of the cKIT signaling pathway. In a murine model of neovascular AMD, intravitreal injection of NN2101 substantially inhibited the SCF/cKIT-mediated choroidal neovascularization (CNV), with efficacy comparable to aflibercept, a vascular endothelial growth factor inhibitor. A combined intravitreal injection of NN2101 and aflibercept resulted in an additive therapeutic effect on CNV. NN2101 neither caused ocular toxicity nor interfered with the early retinal vascular development in Mice. Ocular pharmacokinetic analysis in rabbits indicated that NN2101 demonstrated a pharmacokinetic profile suitable for intravitreal injection. These findings provide the first evidence of the potential use of the anti-cKIT blocking antibody, NN2101, as an alternative or additive therapeutic for the treatment of neovascular AMD.
