Exploiting Inhibitory Siglecs to Combat Food Allergies
Abstract
During year two of this Expansion Award, we have generated new data targeting CD22 on B cells and CD33 on human basophils and mouse mast cells to abrogate food allergies. Under Specific Aim 1, we have generated peanut allergic CC027 mice and characterized their allergic response to peanut allergens for use of STALs inactively sensitized mice with circulating antibodies. Under Specific Aim 2, we generated additional data using our approach of conjugating human CD33L directly to anti-human IgE (alpha IgE-CD33L), without the use of liposomes for scaffolding to inhibit human basophil degranulation and show that the molecule relies on CD33 for its suppressive activity. We report progress towards our goal of using a Xolair (trademark) like anti-IgE antibody to extend the desensitization of mast cells induced by CD33L decorated allergenic nanoparticles (CD33L-STALs). The potential for alpha IgE-CD33L to serve as a universal desensitizing agent is demonstrated using humanized mice sensitized to peanut and ovalbumin (OVA) food allergens, and preventing anaphylaxis upon peanut extract or OVA challenge. A manuscript has been prepared and submitted to the Journal of Allergy and Clinical Immunology in September 2023. In summary, our data continue to show promise for both CD22 and CD33-directed therapeutic approaches for the treatment of food allergies using human cells and mouse models of anaphylaxis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1223167
Entities
People
- James C. Paulson
- Michael Kulis
Organizations
- University of North Carolina at Chapel Hill