# Exploiting inhibitory Siglecs for desensitizing mast cells

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $612,669

## Abstract

PROJECT SUMMARY/ABSTRACT
Unwanted immune responses by mast cells and basophils contribute to the symptoms of allergies and
asthma. In the proposed research we seek to harness members of the Siglec family of inhibitory receptors to
suppress antigen mediated IgE dependent activation and degranulation of mast cells (and basophils), and
desensitize them to subsequent antigen challenge. To this end we will employ Siglec tolerizing antigenic
liposomes (STALs) that display both an antigen and high affinity glycan ligand of a Siglec expressed on mast
cells. When STALs encounter a mast cell pre-sensitized with antigen specific IgE bound to the high affinity
IgE receptor (FcεRI), the glycan ligand will recruit the inhibitory siglec to the immunological synapse. While
liposomes with antigen alone will powerfully activate the cells, the glycan ligand on STALs recruits the
inhibitory siglec blocking activation and degranulation. One of the Siglecs expressed on human mast cells is
CD33 (Siglec-3). We have found that STALs co-displaying antigen and high affinity glycan ligands CD33 can
suppress mast cell degranulation in vitro and in transgenic mice with mast cells expressing human CD33 can
protect against systemic anaphylaxis upon subsequent antigen challenge. Major aims of this project are to
optimize CD33 targeted STALs for suppressing IgE mediated systemic anaphylaxis, in sensitized mouse
models. The goal is to develop an approach to provide sustained protection against antigen mediated allergic
responses mediated by the IgE/FcεRI axis.
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## Key facts

- **NIH application ID:** 10219077
- **Project number:** 5R01AI132790-04
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** JAMES C PAULSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $612,669
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219077

## Citation

> US National Institutes of Health, RePORTER application 10219077, Exploiting inhibitory Siglecs for desensitizing mast cells (5R01AI132790-04). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10219077. Licensed CC0.

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