# Cellular Strategies for Tolerance Induction

> **NIH NIH U19** · EMORY UNIVERSITY · 2022 · $694,450

## Abstract

Renal transplantation represents first-line therapy for patients with ESRD, with the most recent data
documenting significant one-year success rates. However, patients continue to face high 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 greatly
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 mixedchimerism induction (especially in combination with T cell costimulation blockade) and regulatory T cell
(Treg)-based approaches. Both of these therapies hold the promise of fundamentally resetting recipient
immunity in favor of allograft acceptance, and thus provide a direct pathway towards immune toleranceinduction. In this Project, we will explore the following Aims, each designed to advance the use of cellular
therapies for tolerance induction after renal transplantation: Specific Aim #1: To induce immune tolerance
to a renal allograft through the induction of stable, full-spectrum mixed-hematopoietic chimerism in the
setting of T cell costimulation blockade.
Specific Aim #2: To utilize regulatory T cells to induce stable, full-spectrum mixed-chimerism and immune
tolerance during renal transplantation.

## Key facts

- **NIH application ID:** 10609610
- **Project number:** 4U19AI051731-21
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Christian P. Larsen
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $694,450
- **Award type:** 4C
- **Project period:** 2022-08-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609610

## Citation

> US National Institutes of Health, RePORTER application 10609610, Cellular Strategies for Tolerance Induction (4U19AI051731-21). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10609610. Licensed CC0.

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