Spatial control over innate immune activation by amphiphilic nanobiomaterials
Spatial control over the activity of small molecule immune-stimulatory compounds is key in the successful design of potent vaccines and cancer immune-therapeutics. For example, Toll like receptors 7 and 8, which are localized on the endosomal membrane of innate immune cells, recognize viral RNA as natural ligand and triggering causes robust type I interferon responses that are strong mediators of anti-viral and anti-tumoral immune responses. Potent small molecule agonists of TLR7/8 have been discovered, but as many small molecule drugs, suffer from an unwanted pharmacokinetic profile in the context of immune-therapy. Indeed, whereas the primary target of these drugs are innate immune cell subsets in lymphoid organs and/or the tumor microenvironment, they are prone to rapid distribution throughout the body, thereby causing systemic life-threatening inflammation. We show that conjugation of small molecule TLR7/8 agonists to amphiphilic nanobiomaterials alters the pharmacokinetic profile and thus enhances safety by restricting immune activation to secondary lymphoid tissue. This is demonstrated in the context of vaccine design and for cancer immunotherapy. We further demonstrate a key contribution of the colloidal or albumin-binding nature of the resulting nanobiomaterials to achieve lymph node focused immune-stimulation.
Bruno graduated as Chemical Engineer in 2003 from Ghent University where he obtained his PhD in pharmaceutical sciences in 2006 on self-assembly of polyelectrolyte multilayer. This work he was awarded the graduate student award for pharmaceutical technology from the AAPS and the Andreas Deleenheer award from Ghent University. After 2 years of postdoctoral research at Utrecht University (The Netherlands) Bruno returned to the Ghent University. In October 2012 Bruno was appointed as Assistant Professor, in 2017 as Associate Professor, and in February 2019 as Full Professor at the Department of Pharmaceutics at Ghent University. He is currently a recipient of an ERC Consolidator Grant.