Targeting chemokine–glycan interactions: the CellJammer® technology platform

Glycosaminoglycans (GAGs) on the surface of endothelial cells are important co-receptors for chemokines. Immune cells, for instance, follow a chemotactic gradient to reach its source marked by GAG-bound chemokines at the inflammatory hot spot before invading the surrounding tissue. There are several possible ways to therapeutically interfere with chemokine signalling, but almost all neglected so far the pivotal GAG-interactions. We have developed potent and selective anti-inflammatory biopharmaceuticals based on chemokines by increasing their affinity towards GAGs and by knocking out their G-protein coupled receptor (GPCR) activity. These decoy proteins efficiently displace their wild-type counterparts from endothelial surfaces thereby preventing leukocyte migration and thus disease progression. In vivo data strongly support this concept and the first-in-men study with our lead product PA401, an IL-8-based decoy protein, has been initiated late June 2012.