# Engineering Specific Regulatory T Cells to Treat Allergy

> **NIH NIH R21** · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · 2020 · $228,744

## Abstract

Abstract:
Novel therapies to prevent and reverse adverse immune responses are needed in allergy,
autoimmunity, and monogenic diseases. The focus of our lab is to develop and translate
effective therapies to prevent and reverse such adverse immune responses. For example,
allergies to food, venom or pollen affect up to one in five Americans but treatments primarily
involve provision of systemic symptomatic relief and very few offer direct efforts to prevent or
reverse the specific responsiveness. The long-term goal of this project is to develop a
therapeutic approach that safely confers long-lasting protection against allergic disease in an
antigen-specific manner. Regulatory T-cell (Treg) therapy is potentially promising, but
polyclonal Tregs are not specific. Our lab has developed engineered human and mouse
regulatory T cells (Tregs), rendered specific by expression of single chain Fv or T-cell
receptors (TCR) as chimeric antigen receptors (CAR), both of which have shown efficacy in
vitro and in vivo in models of hemophilia and autoimmunity. Recently, we modified this Treg
approach to express antigen on Tregs; these cells, which we term BAR (for B-cell Antibody
Receptor Tregs), can interact and suppress specific B cells via recognition by the B-cell
receptor, an approach that has long-term advantages over non-specific immune modulators or
other CAR approaches. Importantly, BAR Tregs can suppress reactivity in a passive
anaphylaxis model, a result that suggests direct activity of IgE-sensitized mast cells. We
hypothesize that BAR Tregs have potential to treat allergy. In this proposal, we wish to focus
on BAR Tregs because they target the relevant specific B cells or IgE-sensitized mast cells.
Based on our preliminary data that both human and murine BAR Tregs are functional in a
model of allergy to ovalbumin (OVA), our goals are to utilize these BAR Tregs in both active
and passive anaphylaxis models to establish their effect on the IgE response and to follow their
trafficking and persistence, as well as mechanism of action via targeting of IgE-sensitized mast
cells. The results of this study would provide pre-clinical evidence for efficacy leading to clinical
translation of adverse immune responses.

## Key facts

- **NIH application ID:** 9979502
- **Project number:** 1R21AI146687-01A1
- **Recipient organization:** HENRY M. JACKSON FDN FOR THE ADV MIL/MED
- **Principal Investigator:** David William Scott
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,744
- **Award type:** 1
- **Project period:** 2020-04-06 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979502

## Citation

> US National Institutes of Health, RePORTER application 9979502, Engineering Specific Regulatory T Cells to Treat Allergy (1R21AI146687-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9979502. Licensed CC0.

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