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The engineered tetra-valent antibody, ASP4021, fully activates the Tie2 receptor with comparable potency to its natural ligand, angiopoietin-1 by Yukari Koya; Hiromi Nara; Shigenori Yagi; Chihoko Ueno; Masazumi Kamohara is a scholarly article available to read on EtoBox.

What is The engineered tetra-valent antibody, ASP4021, fully activates the Tie2 receptor with comparable potency to its natural ligand, angiopoietin-1 about?

## Abstract Activation of the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor by angiopoietin-1 (Ang1) is critical for vascular stabilization: it promotes survival signal transduction via auto-phosphorylation and reduces vascular permeability by strengthening tight junctions between endothelial cells. Thus, Tie2/Ang1 signaling is a promising therapeutic target for vascular diseases. However, in vivo use of existing Tie2 signaling modulators, such as recombinant Ang1, is restricted by limitations in manufacturability and stability. Here, we present a novel engineered tetra-valent agonistic antibody, ASP4021, which can specifically and fully activate the Tie2 receptor in an equivalent manner to Ang1. ASP4021 induced Tie2 self-phosphorylation and inhibited apoptosis in a human primary endothelial cell line. Additionally, single administration of ASP4021 significantly suppressed mustard-oil-induced vascular permeability in rats. ASP4021 may thus be a potential therapeutic candidate for diseases associated with vascular weakness such as diabetic retinopathy, diabetic macular edema and critical limb ischemia.

Author

Yukari Koya; Hiromi Nara; Shigenori Yagi; Chihoko Ueno; Masazumi Kamohara

Publisher

Research Square Platform LLC

Published

2021

Language

EN