Nature Medicine11, 446 - 449 (2005)
Published online: 27 March 2005; | doi:10.1038/nm1219
A chimeric human-cat fusion protein blocks cat-induced allergy
Daocheng Zhu1, 3, Christopher L Kepley2, 3, Ke Zhang1, 3, Tetsuya Terada1, 3, Takechiyo Yamada1
& Andrew Saxon1
1
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.
2
Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Room 4-115B, McGuire Hall, 1112 East Clay Street, Virginia Commonwealth University, Richmond, Virginia 23298-0263, USA.
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 Fc1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fc-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 Fc-Fel d1 protein also blocked in vivo reactivity in FcRI transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fc-Fel d1 protein alone did not induce mediator release. Chimeric human Fc-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.
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