VT-214 is a secreted glycoprotein that has a molecular weight of ~35 kDa, and unlike other chemokine inhibitors in development, has demonstrated an ability to bind the C-terminal heparin binding domain that is found in all three classes (C, CC and CXC) of human chemokines. VT-214 is a potent inhibitor of inflammatory cell recruitment and is active in vivo at extremely low doses in rabbit, mouse, and rat models of inflammation, including balloon angioplasty induced restenosis, solid organ (renal) transplant, and aortic allograft transplant. VT-214 reduces vascular inflammation as measured by a reduction in both intimal hyperplasia and monocyte/macrophage infiltration into the sites of injury.
Recent studies have confirmed that chemokine oligomerization and binding to glycosaminoglycans are essential for their activity in vivo. Binding of the glycosaminoglycan heparin to chemokines has been found to interfere with the binding of VT-214. In addition, chemokine analogues lacking a heparin-binding domain were no longer able to bind to VT-214 in vitro. Therefore, it is thought that by interfering with the chemokine gradient formation, VT-214 can neutralize the activity of a broad range of chemokines. Importantly, in a mouse model where peritoneal chemokine administration (MCP-1) induces leukocyte recruitment, VT-214 was found to reduce the total number of infiltrating macrophages and T-cells.