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A Fully Human Monoclonal Antibody Targeting cKIT Is a Potent Inhibitor of Pathological Choroidal Neovascularization in Mice

Authors :
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
Source :
Pharmaceutics, Vol 13, Iss 8, p 1308 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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 hypoxic human 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.

Details

Language :
English
ISSN :
19994923
Volume :
13
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.6627a8678c4545eda940d73f04782c85
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics13081308