title: A chimeric human-cat fusion protein blocks cat-induced allergy.
abstract: Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-Fel d1 protein induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release from cat-allergic donors' basophils and sensitized human cord blood-derived mast cells. Such inhibition was associated with altered Syk and ERK signaling. The Fcgamma-Fel d1 protein also blocked in vivo reactivity in FcepsilonRIalpha transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcgamma-Fel d1 protein alone did not induce mediator release. Chimeric human Fcgamma-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.
authors.affiliation: The Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1680, USA. dczhu@ucla.edu
authors.forename: Daocheng
authors.initials: D
authors.lastname: Zhu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Kepley
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terada
authors.forename: Takechiyo
authors.initials: T
authors.lastname: Yamada
authors.forename: Andrew
authors.initials: A
authors.lastname: Saxon
mesh_terms: D000818:Animals; D002415:Cats; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014612:Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C059296:Fel d 1 protein, Felis domesticus