# Siglec-targeted nanoparticles for treating mast cell mediated allergic disease

> **NIH NIH U19** · NORTHWESTERN UNIVERSITY · 2020 · $396,792

## Abstract

PROJECT SUMMARY/ABSTRACT
Unwanted immune responses by mast cells 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
allergen mediated IgE dependent activation and degranulation of human mast cells, and desensitize them to
subsequent antigen challenge. To this end we will employ Siglec tolerizing allergenic liposomes (STALs) that
display both an allergen and synthetic high affinity glycan ligand of a Siglec expressed on mast cells. When
STALs encounter a mast cell pre-sensitized with an allergen specific IgE bound to the high affinity IgE receptor
εRI), 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 is hypothesized to recruit the
inhibitory Siglec and dampen or suppress activation and degranulation. In this project we will focus on two
Siglecs on human mast cells, namely CD33 and Siglec-8. We will assess the impact of STALs for desensitizing
human mast cells in models of passive cutaneous and passive systemic anaphylaxis using transgenic mice
with mast cells expressing a human Siglec (Siglec-8 and CD33) and a human FcεRI receptor, and humanized
mice engrafted with human CD34+ stem cells that populate the mouse with human mast cells. A portion of our
effort will also be devoted to improving the specificity of the synthetic ligand for Siglec-8 and develop a novel
ligand for the Siglec-6 receptor, a mast cell target for Project 1.
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## Key facts

- **NIH application ID:** 9852968
- **Project number:** 5U19AI136443-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** JAMES C PAULSON
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,792
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852968

## Citation

> US National Institutes of Health, RePORTER application 9852968, Siglec-targeted nanoparticles for treating mast cell mediated allergic disease (5U19AI136443-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852968. Licensed CC0.

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