“Accentuate the negative, eliminate the positive”: Engineering allergy therapeutics to block allergic reactivity through negative signaling

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: By targeting the dominant-negative signaling receptor Fc?RIIb expressed on proallergic cells, we have developed 2 novel platforms for the treatment of IgE-mediated allergic disease. First is a genetically engineered bifunctional human fusion protein GE2, which is comprised of the Fc portions of human IgE and IgG1 with an interposed flexible linker designed as a long-term parenteral allergen-nonspecific therapy. GE2 blocks the effector phase of the IgE response in vitro in mice and human subjects and in vivo in the skin and airway and systemically in mice and monkeys. Whether reactivity against human GE2 in human subjects will limit its applicability remains to be determined. The second platform is designed to provide a safer form of allergen-specific immunotherapy and consists of genetically engineered chimeric human Fc?-allergen proteins, with Fc?–Fel d 1 as the prototype. The allergen portion binds to specific IgE on FceRs, whereas the Fc? portion coaggregates inhibitory Fc?RIIb and drives inhibition of allergic reactivity. Fc?–Fel d 1 blocked human mast cell Fel d 1–induced allergic reactivity in vitro and in vivo in murine models while functioning as an immunogen but not as an allergen.

Additional Information

J. Allergy Clin Immunol. 2008 Feb; 121(2):320-5.
Language: English
Date: 2008
IgE therapeutics, immune response modifiers, allergy therapy, Fc?RII, FceRI, mast cells, basophils

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