# Diversity Supplement - Formulation to Generate Tolerance Towards Type 1 Diabetes

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $110,072

## Abstract

ABSTRACT
This submission is a supplement to our parent grant R01DK130225 “Formulation to Generate
Tolerance Towards Type 1 Diabetes”
Parent Abstract: Currently no cure exists for the autoimmune disease Type 1 diabetes (T1D), despite the fact
that the Juvenile Diabetes Research Foundation estimates ~80 individuals are newly diagnosed with the disease,
daily. Due to immune-mediated destruction of insulin-producing β cells, current treatment of T1D is limited to
daily exogenous insulin administration. What is needed are immunotherapies that selectively suppress b cell
autoimmunity for the prevention and treatment of T1D. One approach is the administration of b cell autoantigen
to suppress and tolerize diabetogenic effector T cells. Importantly, this approach avoids effects on protective
immunity seen with other T1D immunotherapies tested in the clinic. Although promising, antigen-based
immunotherapy for T1D has shown only modest clinical results. We have been studying biodegradable,
acetalated dextran microparticles (Ac-DEX MPs) as a polymeric vehicle to deliver antigen and
immunomodulatory drugs. Ac-DEX MPs have a number of properties well suited for the application of
suppressing T cell-mediated autoimmunity and reestablishing self-tolerance. Notably, Ac-DEX MPs can be
manipulated to release cargo in vivo in a tunable manner. We have shown that timing of cargo release has
marked effects on the nature and magnitude of the immune response that is elicited. Furthermore, using this
platform, we have recently shown that delivery of Ac-DEX MPs encapsulating a tolerizing agent (rapamycin) and
a b cell-derived peptide effectively prevents diabetes in an adoptive T cell transfer model of T1D. Accordingly,
the focus of the current proposal is to develop and characterize the tolerogenic properties of Ac-DEX MPs
encapsulating immunomodulatory drugs and b cell-derived peptides as a means to selectively suppress the
diabetogenic response. We hypothesize that the rate of MP degradation plus the co-encapsulation of
immunomodulatory agent enhances the tolerogenic potency of our peptide-based vaccine. To test this
hypothesis, we have proposed two Aims: Specific Aim 1: Encapsulation of rapamycin and antigens in
tunable Ac-DEX particles and optimization of particle system. Here we will establish drug, dosing, and
degradation rate of the microparticles for optimum inhibition of immune response. Specific Aim 2: Evaluation
of Ac-DEX particle formulation and mechanism of tolerance in animal models of T1D. In this aim, we will
evaluate the trafficking of the MPs as related to immune cell uptake, characterizing the underlying immune
responses generated by the formulation, evaluate the protective and therapeutic efficacy of the platform, and
determine the therapy results in loss of acquired immunity.

## Key facts

- **NIH application ID:** 10560761
- **Project number:** 3R01DK130225-02S1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kristy M Ainslie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $110,072
- **Award type:** 3
- **Project period:** 2021-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10560761

## Citation

> US National Institutes of Health, RePORTER application 10560761, Diversity Supplement - Formulation to Generate Tolerance Towards Type 1 Diabetes (3R01DK130225-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10560761. Licensed CC0.

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