Abrogation of allergic reactions by a bispecific antibody fragment linking IgE to CD300a

Ido Bachelet, Ariel Munitz, Francesca Levi-Schaffer

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Initiated and regulated by mast cells, allergic responses are balanced through an intricate network of positive and negative signals. We have recently shown that the inhibitory receptor CD300a is expressed on human mast cells and modulates a large array of their functions. Objective: We sought to evaluate CD300a as a negative regulator of allergic inflammation in vivo by means of a bispecific antibody linking CD300a with IgE. Methods: Bispecific antibody fragments were generated by chemical conjugation of Fab′ fragments of anti-human IgE and CD300a (IE1 H) and anti-mouse IgE and CD300a (IE1 M). IgE-sensitized human mast cells were activated simultaneously with anti-IgE and IE1 H. Phosphorylation of signaling proteins and calcium influx were evaluated by using fluorescence-activated cell sorting. Degranulation was assessed on the basis of tryptase and IL-4 release. IE1 M was administered simultaneously with allergen challenge in 2 murine models of allergic disease. Passive cutaneous anaphylaxis was assessed by means of dye exudation. Experimental airway inflammation was assessed on the basis of tryptase and cytokine content, eosinophilic infiltration, and lung histology (hematoxylin and eosin and periodic acid-Schiff stain). Results: IE1 H potently inhibited IgE-mediated mast cell degranulation in a dose-dependent manner by inhibiting the signaling events induced by FcεRI. IE1 M completely abolished dye exudation in passive cutaneous anaphylaxis. IE1 M abrogated allergic airway inflammation. Conclusion: Our results demonstrate that specific targeting of CD300a on mast cells is a potent strategy for inhibiting allergic reactions. Clinical implications: This work demonstrates a potent approach for the therapy of allergic diseases.

Original languageEnglish
Pages (from-to)1314-1320
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume117
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

Keywords

  • Allergy
  • CD300a
  • bispecific antibody
  • mast cells

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