A research team at the Institute for Basic Science (IBS) has developed a novel antibody that normalizes damaged vessels in patients, offering a  therapeutic antibody mechanism by identifying it in a three-dimensional molecular structure.

The research team expects the study results to help develop therapeutic agents for various diseases that accompany vascular damage, including cancer and sepsis.

Chief Investigator Kim Ho-min of the Center for Biomolecular and Cellular Structure and Director Koh Gou-young of the Center for Vascular Research at IBS led the study,

Blood vessels play a key role in human health as it delivers oxygen and nutrients to cells, transports wastes to excretory organs, and help immune cells to move around. Vascular homeostasis is regulated through the angiopoietin-Tie2 signaling system, a vascular-specific receptor tyrosine kinase pathway essential for vessel development.

However, in diseases such as cancer, sepsis, diabetic retinopathy, and foot ulcer, vascular endothelial cells and supporting cells become destroyed, resulting in serious vascular damage.

Angiopoietin1 protein induces cell surface aggregation by binding to Tie2 receptors in vascular endothelial cells. The process causes Tie2 activation and vascular stabilization. Most Tie2 activation-inducing therapeutics focused on angiopoietin variants through protein engineering, which had low productivity, stability, and short half-life in vivo.

The research team adopted a different way from previous developments of a therapeutic agent that induces Tie2 activation. As a result, researchers succeeded in developing a Tie2 activating antibody, hTAAB, that binds to the Tie2 receptor of vascular endothelium and promotes growth and stabilization.

“The recent finding is a novel discovery that the Tie2 receptor activating antibody induces aggregation of Tie2 in a polygonal shape and activates it,” Chief Investigator Kim said. “This case represents excellent outcomes achieved through cooperation between the two research centers at IBS, and a study showing that basic research and applied sciences are not separated into different fields.”

Director Koh also said, “We expect our study results will be linked to future developments of treatments for various diseases caused by vascular abnormalities by verifying efficacy in animal models.”

The study results were published in Nature Communications on Monday.