Systemic administration of an Fcgamma-Fc(epsilon)-fusion protein in house dust mite sensitive nonhuman primates

Crosslinking Fc(epsilon)RI and FcgammaRIIB receptors inhibits mast cell and basophil activation, decreasing mediator release. In this study, a fusion protein incorporating human Fcgamma and Fc(epsilon) domains, hGE2, was shown to inhibit degranulation of human mast cells and basophils, and to exhibi...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 128(2008), 3 vom: 15. Sept., Seite 340-8
1. Verfasser: Van Scott, Michael R (VerfasserIn)
Weitere Verfasser: Mertsching, Elisabeth, Negrou, Ella, Miles, Jeremy, Stallings, Howard W 3rd, Graff, Candace, Kehry, Marilyn R
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2008
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Allergens FCGR2B protein, human Receptors, IgE Receptors, IgG Recombinant Fusion Proteins
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520 |a Crosslinking Fc(epsilon)RI and FcgammaRIIB receptors inhibits mast cell and basophil activation, decreasing mediator release. In this study, a fusion protein incorporating human Fcgamma and Fc(epsilon) domains, hGE2, was shown to inhibit degranulation of human mast cells and basophils, and to exhibit efficacy in a nonhuman primate model of allergic asthma. hGE2 increased the provocative concentration of dust mite aeroallergen that induced an early phase asthmatic response. The treatment effect lasted up to 4 weeks and was associated with reduction in the number of circulating basophils and decreased expression of Fc(epsilon)RI on repopulating basophils. Repeat hGE2 dosing induced production of serum antibodies against human Fcgamma and Fc(epsilon) domains and acute anaphylaxis-like reactions. Immune serum induced histamine release from human IgE or hGE2-treated cord blood-derived mast cells and basophils in vitro. These results indicate that repeat administration with hGE2 induced an antibody response to the human molecule that resulted in activation rather than inhibition of allergic responses 
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650 7 |a FCGR2B protein, human  |2 NLM 
650 7 |a Receptors, IgE  |2 NLM 
650 7 |a Receptors, IgG  |2 NLM 
650 7 |a Recombinant Fusion Proteins  |2 NLM 
700 1 |a Mertsching, Elisabeth  |e verfasserin  |4 aut 
700 1 |a Negrou, Ella  |e verfasserin  |4 aut 
700 1 |a Miles, Jeremy  |e verfasserin  |4 aut 
700 1 |a Stallings, Howard W  |c 3rd  |e verfasserin  |4 aut 
700 1 |a Graff, Candace  |e verfasserin  |4 aut 
700 1 |a Kehry, Marilyn R  |e verfasserin  |4 aut 
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