University of Jeddah
Title: Use of nanoengineered surfaces for intracellular drug delivery via simultaneous engagement of inhibitory and stimulating receptor on mast cells and basophils
Waalla Alelwani has completed her PhD in July 2015 from the University of Nottingham at School of Pharamcy. She is Vice President of the Jeddah University Centre for Scientific and Medical research as well as working in the University as assistant professor.
The production of chemical mediators such as histamine from activated mast cells and basophils, which is triggered by aggregation of the high affinity IgE receptor, is involved in many inflammatory and in particular in Type I allergic reactions. Current strategies for the treatment of allergy target the histamine receptors which mediate the effects of histamine or other mediators such as leukotrienes and cytokines in the tissues (e.g. Montelukast, H1-antagonists, Nuvance), or alternatively target the IgE molecule itself (Omalizumab). It has been known for a number of years that degranulation of mast cells and basophils can be inhibited via simultaneous aggregation (co-crosslinking) of the high affinity IgE receptor (FcεRI) and the low affinity IgG receptor (FcγRIIB).We propose to design a novel immunotherapy approach for the treatment of allergy and other diseases related to mast cell and basophil activation which takes advantage of the most recent advances in biomedical nanotechnology. The strategy consists in exploiting the high affinity and selectivity of IgE for FcεRI to deliver drugs (e.g. signal transduction inhibitors, or shRNA) intracellularly without causing basophil or mast cell activation. This is to be achieved by simultaneous engagement of FcεRI and FcγRIIB using defined stoichiometries and orientations of the antibodies to enhance interaction with their respective receptors. Several difficulties caused by incompatibility of assay buffers with the nanoparticles had to be solved. Additionally, the binding affinity between the Fc region of human IgG1 and FcγRIIB needed to be increased by engineering an Fc region with multiple amino acids substitutions.