Anti-angiogenic collagen IV-derived peptide target engagement with αvβ3 and α5β1 in ocular neovascularization models

Raquel Lima e Silva; Adam C. Mirando; Stephany Y. Tzeng; Jordan J. Green; Aleksander S. Popel; Niranjan B. Pandey; Peter A. Campochiaro

iScience (Feb 2023)

Anti-angiogenic collagen IV-derived peptide target engagement with αvβ3 and α5β1 in ocular neovascularization models

Raquel Lima e Silva,
Adam C. Mirando,
Stephany Y. Tzeng,
Jordan J. Green,
Aleksander S. Popel,
Niranjan B. Pandey,
Peter A. Campochiaro

Affiliations

Raquel Lima e Silva: Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Adam C. Mirando: AsclepiX Therapeutics, Inc., Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Stephany Y. Tzeng: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Jordan J. Green: Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Aleksander S. Popel: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Niranjan B. Pandey: AsclepiX Therapeutics, Inc., Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Peter A. Campochiaro: Department of Ophthalmology and The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 2
p. 106078

Abstract

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Summary: AXT107, a collagen-derived peptide that binds integrins αvβ3 and α5β1 with high affinity, suppresses vascular endothelial growth factor (VEGF) signaling, promotes angiopoietin 2-induced Tie2 activation, and suppresses neovascularization (NV) and vascular leakage. Immunohistochemical staining for αvβ3 and α5β1 was markedly increased in NV compared with normal retinal vessels. After intravitreous injection of AXT107, there was no staining with an anti-AXT107 antibody on normal vessels but robust staining of NV that co-localized with αvβ3 and α5β1. Likewise, after intravitreous injection, fluorescein amidite-labeled AXT107 co-localized with αvβ3 and α5β1 on NV but not normal vessels. AXT107 also co-localized with αv and α5 at cell-cell junctions of human umbilical vein endothelial cells (HUVECs). AXT107-integrin binding was demonstrated by ex vivo cross-linking/pull-down experiments. These data support the hypothesis that AXT107 therapeutic activity is mediated through binding αvβ3 and α5β1 which are markedly upregulated on endothelial cells in NV providing selective targeting of diseased vessels which has therapeutic and safety benefits.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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