[논문]Preclinical Efficacy and Safety of VEGF-Grab, a Novel Anti-VEGF Drug, and Its Comparison to Aflibercept

Hong, Hye Kyoung; Park, Young Joo; Kim, Duk Ki; Ryoo, Na-Kyung; Ko, You-Jin; Park, Kyu Hyung; Kim, Ho Min; Woo, Se Joon

doi:10.1167/iovs.61.13.22

[해외논문] Preclinical Efficacy and Safety of VEGF-Grab, a Novel Anti-VEGF Drug, and Its Comparison to Aflibercept 원문보기

Investigative ophthalmology & visual science, v.61 no.13, 2020년, pp.22 -

Hong, Hye Kyoung (Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea) , Park, Young Joo (Department of Ophthalmology, Kangwon National University Hospital, Chuncheon, Korea) , Kim, Duk Ki (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea) , Ryoo, Na-Kyung (Department of Ophthalmology, Veterans Health Service Medical Center, Seoul, Korea) , Ko, You-Jin (Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea) , Park, Kyu Hyung (Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea) , Kim, Ho Min (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea) , Woo, Se Joon (Department of Ophthalmology, Seoul National University Bundang Hospital, Seongnam, Korea)

Abstract ▼ AI-Helper

PurposeVEGF-Grab is a novel anti-vascular endothelial growth factor (VEGF) candidate drug with higher affinity to both VEGF and placental growth factor (PlGF) compared to aflibercept. We investigated the preclinical efficacy of VEGF-Grab for ophthalmic therapy and compared it to that of aflibercept.MethodsThe in vitro anti-VEGF efficacy of VEGF-Grab was determined using VEGF-induced cell proliferation/migration and tube formation assays. The in vivo antiangiogenic efficacy of intravitreal injection of either VEGF-Grab or aflibercept was evaluated using murine models of ocular angiogenesis: mouse oxygen-induced retinopathy (OIR) and rat laser-induced choroidal neovascularization (CNV). The in vivo retinal toxicity in the mouse eye resulting from the injection of either drug was evaluated with light and electron microscopy.ResultsVEGF-Grab showed greater inhibition of VEGF-induced cell proliferation/migration than aflibercept, but it showed comparable inhibition of tube formation in vitro. In the in vivo OIR model, VEGF-Grab showed a comparable suppression of retinal neovascularization compared to aflibercept. Additionally, VEGF-Grab showed an efficacy similar to that of aflibercept in terms of CNV inhibition in the laser-induced CNV model. Histology and transmission electron microscopy showed no significant signs of toxicity in the mouse retina at 7 and 30 days following the intravitreal injection of VEGF-Grab or aflibercept.ConclusionsCompared to aflibercept, VEGF-Grab presented comparable in vivo antiangiogenic efficacy and superior in vitro anti-VEGF activity. The retinal safety profiles were comparable for the two drugs. Considering its known higher binding affinity to VEGF and PlGF compared to aflibercept, VEGF-Grab could be a potential candidate drug for neovascular retinal diseases and an alternative to aflibercept.

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