# Immunoengineered nanotechnology for targeted expansion of regulatory T cells

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $421,107

## Abstract

PROJECT SUMMARY/ABSTRACT
Development of an immunoengineered technology to selectively stimulate and expand regulatory T (TReg) cells
in vivo would be transformative for autoimmune disease treatment and transplantation medicine. Extensive
evidence has established that adoptively transferred TReg cells, and in particular antigen-specific TReg cells,
effectively suppress pathogenic autoimmune activity to combat disease. However, logistical and manufacturing
complications as well as safety concerns associated with ex vivo expanded T cells impede clinical adoption of
this approach. Thus, there is an unmet medical need for an off-the-shelf, non-cellular platform that activates
antigen-specific TReg cells to manifest immunosuppression directly in patients. The interleukin-2 (IL-2) cytokine
potently activates TReg cells, and has proven to be a promising alternative to adoptive TReg cell transfer. However,
IL-2 concurrently stimulates activation of effector cells, resulting in harmful off-target effects and toxicities. Co-
administration of IL-2 in complex with certain anti-cytokine antibodies preferentially activates and expands TReg
over effector cells, but concerns about cytokine/antibody complex dissociation hinder the therapeutic
development of this approach. Furthermore, IL-2 treatment induces non-specific expansion of TReg cells, with
limited enrichment of therapeutically superior antigen-specific cells.
 This proposal aims to develop a robust and versatile platform that activates antigen-specific TReg cells
and simultaneously inhibits the function of pathogenic autoreactive T cells. This technology synthesizes, for the
first time, three design approaches: (1) Selective delivery of IL-2 to TReg cells; (2) Stimulation of antigen-specific
TReg cells using artificial antigen-presenting cells (aAPCs); and (3) Localized release of an immunosuppressive
drug to prevent effector T cell activation. The novel platform, denoted TolAPC, comprises nanoparticles coated
with self peptide-loaded major histocompatibility complex (MHC) as well as a stabilized single-chain fusion format
of an IL-2/antibody complex that selectively promotes TReg expansion. These particles are also engineered for
controlled release of the immunosuppressive drug rapamycin. TolAPCs will be characterized in vitro and in vivo
to assess selective expansion of TReg cells that can suppress pathogenic self-reactive effector T cells. They will
also be therapeutically evaluated in autoimmune disease studies in mice. As a model system, TolAPC activity
will be assessed in type 1 diabetes (T1D), a chronic autoimmune disease that is a growing threat to global health
with incidence rising at an alarming rate of 3% annually. The modularity of the TolAPC platform will allow for
ready extension to a host of applications in autoimmune disease treatment and transplant tolerance through
substitution of the antigen specificity. Overall, our targeted immunomodulatory nanotechnology will serve as a
powerful a...

## Key facts

- **NIH application ID:** 10134337
- **Project number:** 5R01EB029455-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jamie Berta Spangler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,107
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134337

## Citation

> US National Institutes of Health, RePORTER application 10134337, Immunoengineered nanotechnology for targeted expansion of regulatory T cells (5R01EB029455-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10134337. Licensed CC0.

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