# Development of a Regulatory T Cell Mimetic for Tolerance Induction in Skin Transplantation

> **NIH NIH R21** · DUQUESNE UNIVERSITY · 2020 · $142,957

## Abstract

Each year in the United States there are close to 30,000 hospitalizations in specialized burn centers. Many of
these patients benefit from human skin allografts as temporary wound closure to promote rapid healing. Skin
allografts, being highly immunogenic, begin to lose viability shortly after transplantation and are completely
rejected by cytotoxic T cells within two weeks. Extending skin allograft survival is an unmet medical need
because it will prolong the duration in which burn victims are protected from dehydration and infection.
Regulatory T cells (Treg) have the potential to prolong the viability of skin allografts, but adoptive cell therapy
of Treg is not feasible in urgent care settings. Systemic infusion of the principal Treg inhibitory molecules,
namely TGF-, IL-10, and CTLA-4 (TIC), is complicated by off-target toxicities and the different
pharmacokinetics of the agents. To address this need, we seek to develop a versatile platform on which TIC
are optimized spatiotemporally for prolonging the survival of skin allografts.
In this project we propose to deliver TIC simultaneously and locally into skin allografts established on full-MHC
mismatched mice. The Treg mimicking strategy entails formulating TIC into an injectable by intermixing with
novel bioaffinity amphiphilic peptides, generating a gel in which Fc-fusion proteins can be loaded. The
multivalent, multifunctional (“multiplexing”) system will enforce a powerful multi-pronged immunosuppression at
the transplant site by cross-linking TGF- and IL-10 receptors, as well as B7 molecules on target leukocytes.
Three specific aims will be carried out to delineate the cellular and molecular mechanisms of the strategy. The
first task is to optimize the dose combination of TIC with respect to raising Treg to Th1 ratio in an allogeneic
skin explant T cell co-culture system. In the second task, we will validate the biocompatibility of the materials
system. In the third task, we will evaluate the capacity of muxTIC to steer T cells toward suppressive
phenotypes in vivo.
The public health impact centers on leveraging an enabling technology by which burn care can be improved.
Given the in vivo transplant model at hand and the biomaterials tools we have developed, our team is uniquely
poised to advance the novel strategy. The materials platform is versatile; Fc-fusion proteins or antibodies
targeting other pathways can be displayed, thereby increasing the scope of the modulation. The broader
impact is that the data generated will set the stage for testing multiplexed Treg factors in vascularized
composite allografts (VCA) transplantation in which the skin is a primary driver of immune rejection.

## Key facts

- **NIH application ID:** 9867640
- **Project number:** 5R21AI139828-02
- **Recipient organization:** DUQUESNE UNIVERSITY
- **Principal Investigator:** Wilson S Meng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $142,957
- **Award type:** 5
- **Project period:** 2019-02-06 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9867640

## Citation

> US National Institutes of Health, RePORTER application 9867640, Development of a Regulatory T Cell Mimetic for Tolerance Induction in Skin Transplantation (5R21AI139828-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9867640. Licensed CC0.

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