# Engineering biomimetic artificial antigen presenting cells for Type 1 Diabetes immunotherapy

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2021 · $41,874

## Abstract

Project Summary
 The overall goal of this project is to design and implement a biomimetic artificial antigen presenting cell
platform to treat Type 1 Diabetes (T1D). T1D is a life-threatening autoimmune disease affecting over 1 million
Americans that occurs when the immune system destroys insulin-producing beta islet cells in the pancreas,
requiring lifelong insulin replacement therapy and greatly increasing the patient’s risk of comorbidities. New
treatments that halt disease and establish tolerance toward beta islets are therefore desirable. One of the most
promising strategies for tolerance induction is the enhancement of regulatory T cells (Tregs). Tregs are powerful
mediators of tolerance toward self-antigens but are often impaired in T1D, and therapies that strengthen their
numbers and restore their function are needed. Artificial antigen presenting cells (aAPCs) directly engage and
modulate T cells via Signal 1, 2, and 3 proteins conjugated to the surface or encapsulated within a particle and
have the capacity to influence Treg populations. However, the vast majority of aAPCs have been designed to
activate cytotoxic T cells for cancer immunotherapies and have not been widely explored in a tolerogenic context.
Current “tolerogenic” aAPCs lack critical factors supporting Treg induction and expansion and pose a risk of
exacerbating the anti-diabetes immune response.
 We have successfully demonstrated that an aAPC platform can be used to induce Tregs. We showed
that altering material properties of the aAPC core improved protein conjugation to the surface of the particle,
giving it potential as an “off-the-shelf” therapy that can be administered directly in vivo. The aAPC core also
supported encapsulation of critical Treg induction factor TGF-β, and a single dose of these aAPCs given to mice
led to polarization of the in vivo T cell repertoire towards Tregs. We therefore hypothesize that encapsulated
and surface-bound tolerogenic cues are critical for modulating Treg populations to induce islet-specific tolerance.
We also hypothesize that aAPC-mediated presentation of an autoreactive insulin peptide in the context of these
additional tolerogenic cues will mediate enhanced aAPC-based Treg induction and expansion in vivo in a mouse
diabetes model. In Specific Aim 1, we will evaluate the capabilities of aAPC with encapsulated and surface-
conjugated signal 1, 2 and 3 molecules to induce Tregs. In Specific Aim 2, we will investigate the capacity of
aAPC with a surface-conjugated IL-2 immunocytokine to expand Treg populations. In Specific Aim 3, we will
analyze the functionality of aAPC-modulated Tregs. In Specific Aim 4, we will determine the potential of aAPCs
to induce tolerance in a mouse model of spontaneous diabetes. The contributions of the present proposal are
significant because it will be the first study to utilize two distinct aAPCs to treat T1D through 1) induction and 2)
expansion of Treg populations, allow for direct comparison of the ...

## Key facts

- **NIH application ID:** 10140956
- **Project number:** 1F31AI152471-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kelly Rhodes
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,874
- **Award type:** 1
- **Project period:** 2021-01-15 → 2022-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140956

## Citation

> US National Institutes of Health, RePORTER application 10140956, Engineering biomimetic artificial antigen presenting cells for Type 1 Diabetes immunotherapy (1F31AI152471-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10140956. Licensed CC0.

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