title: A bispecific antibody against human IgE and human FcgammaRII that inhibits antigen-induced histamine release by human mast cells and basophils.
abstract: BACKGROUND
  FcgammaRIIB are low-affinity immunoglobulin (Ig)G receptors that we previously demonstrated to negatively regulate IgE-induced mast cell activation when coaggregated with FcepsilonRI. Here, we engineered and characterized a bispecific reagent capable of coaggregating FcgammaRIIB with FcepsilonRI 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 FcgammaRII. This molecule was used to coaggregate FcepsilonRI with FcgammaRII 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 FcepsilonRI, with inhibitory receptors, such as FcgammaRIIB, that are constitutively expressed by mast cells and basophils.
authors.affiliation: Tanox Inc., Houston, TX, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Tam
authors.forename: S
authors.initials: S
authors.lastname: Demissie
authors.forename: D
authors.initials: D
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Daëron
mesh_terms: D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology* / Q000502:physiology; D001491:Basophils / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D006633:Histamine Antagonists / Q000276:immunology / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology; D011940:Receptor Aggregation / Q000276:immunology / Q000502:physiology; D017455:Receptors, IgE / Q000187:drug effects / Q000276:immunology; D017452:Receptors, IgG / Q000187:drug effects / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000941:Antigens; C445323:FCGR2A protein, human; C499173:FCGR2B protein, human; D006633:Histamine Antagonists; D017455:Receptors, IgE; D017452:Receptors, IgG; D007073:Immunoglobulin E