Exploiting Inhibitory Siglecs to Combat Food Allergies

Abstract

During this first year of the award, we were able to produce important data, develop a new tool to track allergen-specific B cells, and generate two humanized mouse models. We demonstrated that Ah2 STALs targeting CD22 on B cells can prevent IgE production and allergic reactions with only a single injection in mice. We also demonstrated that Ah2 STALs targeting CD33 on human mast cells and basophils can prevent degranulation in cell culture experiments. A novel tool, Ah2 tetramer, was produced to quantify numbers of allergen-specific B cells in mice. A model to test Ah2 STALs as a therapy was developed in which nave mice were adoptively transferred memory B and T cells from peanut allergic mice. The resulting mice make robust levels of Ah2-IgE and experience anaphylaxis upon challenge. This model will be used to test STALs as a therapy to deplete memory B cells. Furthermore, two novel transgenic mouse models were generated, one expresses human CD22 on B cells and the other expresses human CD33 on mast cells. These models are vital to our proposed research.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2017
Accession Number
AD1048779

Entities

People

  • Matthew S Macauley
  • Michael Kulis

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Allergens
  • Allergy And Immunology
  • Anaphylaxis
  • Antigens
  • Blood
  • Cells
  • Culture Techniques
  • Department Of Defense
  • Granulocytes
  • Immune System
  • Lymphocytes
  • Mast Cells
  • Medical Personnel
  • Production
  • Students
  • Targeting
  • Tetramers

Fields of Study

  • Biology
  • Medicine

Readers

  • Allergy and Immunology.
  • Oncology (Cancer Research).