title: Inhibition of ongoing allergic reactions using a novel anti-IgE DARPin-Fc fusion protein.
abstract: BACKGROUND
  Aggregation of the high-affinity IgE receptor (FcεRI) with the low-affinity IgG receptor (FcγRIIb) on basophils or mast cells has been shown to inhibit allergen-induced cell degranulation. Molecules cross-linking these two receptors might therefore be of interest for the treatment of allergic disorders. Here, we demonstrate the generation of a novel bispecific fusion protein efficiently aggregating FcεRI-bound IgE with FcγRIIb on the surface of basophils to prevent pro-inflammatory mediator release.
  
  
  METHODS
  Alternative binding molecules recognizing receptor-bound human IgE were selected from DARPin (designed ankyrin repeat protein) libraries. One of the selected DARPins was linked to the Fc-part of a human IgG(1) antibody for binding to FcγRIIb.
  
  
  RESULTS
  The resulting anti-IgE DARPin-Fc fusion protein was not anaphylactogenic and inhibited allergen-induced basophil activation in whole blood assays. Both binding moieties of the fusion protein, namely the anti-IgE DARPin as well as the IgG(1) Fc-part, were required to achieve this inhibitory effect. Most importantly, inhibition was faster and more efficient than with Omalizumab, a humanized anti-IgE antibody currently used for the treatment of severe asthma.
  
  
  CONCLUSIONS
  This novel anti-IgE DARPin-Fc fusion protein might represent a potential drug candidate for preventive or immediate treatment of allergic reactions.
authors.affiliation: University Institute of Immunology, University of Bern, Inselspital, Bern Molecular Partners AG, Zürich-Schlieren, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Eggel
authors.forename: P
authors.initials: P
authors.lastname: Buschor
authors.forename: M J
authors.initials: MJ
authors.lastname: Baumann
authors.forename: P
authors.initials: P
authors.lastname: Amstutz
authors.forename: B M
authors.initials: BM
authors.lastname: Stadler
authors.forename: M
authors.initials: M
authors.lastname: Vogel
mesh_terms: D000485:Allergens / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000276:immunology; D015550:Cell Degranulation / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: C472289:ANKRD23 protein, human; D000485:Allergens; D000888:Antibodies, Anti-Idiotypic; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C026408:anti-IgE antibodies; D007073:Immunoglobulin E