June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
A Novel Tie2 activating monoclonal antibody ameliorates the lesion of choroidal neovascularization in monkey and mouse
Author Affiliations & Notes
  • Eun-Ah Lee
    R&D center, PharmAbcine, Daejeon, Korea (the Republic of)
  • Beom Yong Park
    R&D center, PharmAbcine, Daejeon, Korea (the Republic of)
  • Nuri Kang
    R&D center, PharmAbcine, Daejeon, Korea (the Republic of)
  • Cheon Ho Park
    R&D center, PharmAbcine, Daejeon, Korea (the Republic of)
  • Woen Sup Lee
    R&D center, PharmAbcine, Daejeon, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Eun-Ah Lee, Pharmabcine (E); Beom Yong Park, Pharmabcine (E); Nuri Kang, Pharmabcine (E); Cheon Ho Park, Pharmabcine (E); Woen Sup Lee, Pharmabcine (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2021, Vol.62, 638. doi:
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    • Get Citation

      Eun-Ah Lee, Beom Yong Park, Nuri Kang, Cheon Ho Park, Woen Sup Lee; A Novel Tie2 activating monoclonal antibody ameliorates the lesion of choroidal neovascularization in monkey and mouse. Invest. Ophthalmol. Vis. Sci. 2021;62(8):638.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Tie2 receptor is mainly expressed in endothelial cells that modulates angiogenesis with angiopoietins (Ang) binding. VEGF neutralizing molecules were approved to treat neovascular ocular diseases but there still is a great need to develop therapeutic agents to treat the patients who do not respond well to anti-VEGF drugs. We recently isolated a Tie2 activating antibody, PMC-403 and are evaluated its potential therapeutic potential to treat neovascular diseases.

Methods : Experimental CNV was induced by laser photocoagulation in C57BL/6 mice and in rhesus monkeys. The animals received IVT administration of aflibercept or PMC-403 and the dose dependent responses were measured in multiple assays: 1) FFA, OCT and ERG were evaluated. 2) The number of leakage spots, the percent changes of leakage area, and the maximum retinal thickness of laser-burned spots were evaluated. 3) In the monkey CNV model, the level of mRNA expression of 10 genes related to angiogenesis and inflammation was measured.

Results : In similar to Ang1, PMC-403 activated Foxo-1 phosphorylation, inhibited VEGFR-2 phosphorylation, and reduced the Survivin expression in HUVEC cells. In a mouse CNV model, PMC-403 reduced the thickness and the leakage of retinal blood vessels comparable to aflibercept in accompanied with improvement of the sensitivity of optic nerves. In a monkey CNV models, PMC-403 improved retina thickness and vessel leakage but the response rate was slower in comparison to aflibercept. Interestingly, PMC-403 showed better responses in sensitivity of optic nerves than aflibercept with decreased level of pro-angiogenesis genes such as Ang2, VEGF, PlGF, and PDGF. In addition, the level of pericyte in retina was dramatically increased by PMC-403 without inflammation.

Conclusions : PMC-403 improved sensitivity of optic neurons in animal CNV models through a normalization of leaky blood vessels. These data strongly support the notion that PMC-403 stabilizes retinal and choroidal blood vessels and it can be developed as an effective therapeutic agent to treat a wide variety of retinal and choroidal vascular disorders.

This is a 2021 ARVO Annual Meeting abstract.

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