Novel IgE Inhibitors for the Treatment of Food Allergies

Abstract

IgE antibodies bind the high affinity IgE Fc receptor (FceRI), found primarily on mast cells and basophils, and trigger inflammatory cascades of the allergic response. Inhibitors of IgE:FceRI binding have been identified and an anti-IgE therapeutic antibody (omalizumab) is used to treat severe allergic asthma and is being used experimentally for the treatment of food allergies. However, improved therapeutics are needed for the treatment of allergies. We are taking a two-pronged approach to developing improved therapeutics. The first approach is based on our observations that a novel class of anti-IgE inhibitors (DARPins), which can actively take apart receptor complexes, exhibits improved therapeutic potency in a mouse passive cutaneous anaphylaxis model. We propose to develop novel antibody therapeutics with this disruptive activity using a systematic set of experiments. In our second approach, we are pursuing the identification of small molecule inhibitors of the IgE:receptor interaction, since this would potentially allow for the treatment of a broader patient population. We have developed and implemented novel assay tools and approaches to enable the discovery of small molecule inhibitors. We feel that both approaches have significant and complementary value and we have made good progress in our research in both areas during the past year.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2017
Accession Number
AD1061923

Entities

People

  • Theodore Jardetzky

Organizations

  • Stanford University

Tags

DTIC Thesaurus Topics

  • Allergic Diseases
  • Allergy And Immunology
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Crystal Structure
  • Crystals
  • Department Of Defense
  • Diseases And Disorders
  • Dissociation
  • Inhibition
  • Inhibitors
  • Lead Compounds
  • Molecules
  • Plastic Explosives
  • Small Molecules
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Allergy and Immunology.
  • Immunology
  • Oncology