A bispecific antibody against human IgE and human FcγRII that inhibits antigen-induced histamine release by human mast cells and basophils

Authors


Sun W. Tam
Charles River Laboratories
57 Union Street
Worcester, MA 01608
USA

Abstract

Background:  FcγRIIB are low-affinity immunoglobulin (Ig)G receptors that we previously demonstrated to negatively regulate IgE-induced mast cell activation when coaggregated with FcɛRI. Here, we engineered and characterized a bispecific reagent capable of coaggregating FcγRIIB with FcɛRI on human mast cells and basophils.

Methods:  A bispecific antibody was constructed by chemically crosslinking one Fab’ fragment against human IgE and one Fab’ fragment against human FcγRII. This molecule was used to coaggregate FcɛRI with FcγRII on human mast cells and basophils sensitized with human IgE antibodies, and the effect of coaggregation was examined on mediator release upon challenge with specific antigen.

Results:  When used under these conditions, this bispecific antibody not only failed to trigger the release of histamine by IgE-sensitized cells, but it also prevented specific antigen from triggering histamine release. Comparable inhibitions were observed with mast cells and basophils derived in vitro from cord blood cells and with peripheral blood basophils.

Conclusions:  The bispecific antibody described here is the prototype of similar molecules that could be used in new therapeutic approaches of allergic diseases based on the coaggregation of activating receptors, such as FcɛRI, with inhibitory receptors, such as FcγRIIB, that are constitutively expressed by mast cells and basophils.

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