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

Crosslinking Fc epsilon RI and Fc gamma RIIB receptors inhibits mast cell and basophil activation, decreasing mediator release. In this study, a fusion protein incorporating human Fc gamma 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 tasted 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 Fc gamma 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. (C) 2008 Elsevier Inc. All rights reserved.