# Cellular Strategies for Tolerance Induction

> **NIH NIH U19** · EMORY UNIVERSITY · 2020 · $996,881

## Abstract

ABSTRACT:
Renal transplantation represents first-line therapy for patients with end-stage renal disease, with the most
recent data documenting high one-year success rates. However, patients continue to face significant morbidity
and mortality after transplant, both from chronic allograft rejection and from the toxicities associated with
standard immunosuppressive regimens. Given these dual risks, the ultimate goal in this field is the induction of
immune tolerance after transplantation, which promises life-long acceptance of an allograft, without the need
for ongoing immunosuppression and importantly, with preservation of protective immunity. While novel
pharmacologic and antibody-based therapies represent real promise in terms of prolonging allograft survival
and reducing off-target toxicities, murine studies strongly suggest that the most robust strategies for inducing
immune tolerance incorporate cellular therapies, including both regulatory T cell-based approaches and mixed-
chimerism induction (especially in combination with T cell costimulation blockade). Both of these therapies
hold the promise of fundamentally resetting recipient immunity in favor of allograft acceptance, and thus
providing a direct pathway towards immune tolerance for renal transplant recipients. In this proposal, we will
investigate the tolerance-induction potential of both Treg- and Mixed-Chimerism-based cellular therapies
through the following Aims: Aim 1: To engineer an optimally suppressive regulatory T cell product, able to
provide allograft-specific immune tolerance after renal transplantation. Aim 2: To induce immune tolerance to
a renal allograft through the induction of stable, multilineage mixed-hematopoietic chimerism with preservation
of protective immunity in the setting of T cell costimulation blockade. The deliverables for this Project include
the development of two highly promising tolerance-induction strategies for clinical translation, which, if
successful, could change clinical practice in renal transplantation.

## Key facts

- **NIH application ID:** 9988349
- **Project number:** 5U19AI051731-19
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Andrew B Adams
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $996,881
- **Award type:** 5
- **Project period:** 2002-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988349

## Citation

> US National Institutes of Health, RePORTER application 9988349, Cellular Strategies for Tolerance Induction (5U19AI051731-19). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9988349. Licensed CC0.

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