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Doron Melamed - Fc-E is a novel compound for developing drugs to abolish allergies.

Allergies affect about 40% of the population in developed world. Allergy may result in a local hypersensitivity response, but often develops into a severe systemic reaction that may lead to anaphylaxis and even death. IgE antibodies are key mediators of allergies through binding to the FcεR1 on the surface of mast cells and basophils. There is a serious shortage in drugs to treat severe allergies. In fact, the only available medication is omalizumab, which targets free IgE in plasma, but this drug is not effective in a large population, often associated with adverse effects and many of the patients develop drug-resistance. Hence, in a market share of over 30 billion USD/year in USA alone, innovative approaches to abolish and/or treat allergies are necessary. We developed an Fc-E compound molecule that is capable to bind and cap the FceR1 and to repress in vitro IgE-mediated allergic response. We propose to validate the in vitro results and to establish it in a mouse model of food allergy. We also plan to use the Fc-E fragment as a platform to deplete FceR1-expressing cells in vivo. We will fuse the Fc-E with the “kill-me” signaling ligand RAE1, which is recognized by NKG2D receptor on cytotoxic NK and CD8+ T cells. These developments confer a novel umbrella of new treatments for severe allergies, approaching from molecular and cellular directions. We plan that this study shall be used as proof of principle that will be extended for construction of human analogues capable abolishing allergies in human.

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