# Defining the T Cell Mediators of Clinical Response in Chronic GVHD

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2024 · $454,998

## Abstract

Project 1: Defining the T Cell Mediators of Clinical Response in Chronic GVHD
Abstract:
Chronic graft versus host disease (cGVHD) represents the major cause of morbidity and late mortality after
hematopoietic stem cell transplantation (HCT). While multiple innate and adaptive immune cell populations
contribute to its’ pathophysiology, donor T cells orchestrate cGVHD at all stages, either through their direct
effects, or through their influence on other cell populations. However, despite detailed information about the
mechanisms controlling cGVHD derived from mouse models, and the development of several new clinical
therapeutics, the rates of complete response (CR) remain low: most patients demonstrate only a partial
response to therapy, and many have therapy-refractory cGVHD. Moreover, there is a critical lack of
information about what determines clinical response in individual patients treated for cGVHD. To make
breakthroughs in our understanding of the pathogenesis of human cGVHD and to prioritize the next generation
of therapeutics, we must (1) Accurately define the immune pathways that are active in patients who ultimately
develop cGVHD and (2) Determine the mechanisms of both success and failure of cGVHD treatment regimens
at the level of the individual patient. To accomplish these goals, this Project will complete the following Specific
Aims. In Aim 1, we will identify Risk Assignment immune profiles for cGVHD at Day +100. In Aim 2, we will
determine the evolution of treatment-responsive versus -resistant immune profiles in patients with cGVHD. In
Aim 3 we will investigate the impact of gene modification of Tregs based on completed trajectory analyses from
responders versus non-responders to low-dose IL-2, in order to create an optimized cellular therapeutic to control
cGVHD. By accomplishing these Aims, this Project promises to identify the molecular networks that predict
cGVHD, and those associated with response or resistance to cGVHD therapies, thereby paving the way for a
new era of successful prevention and treatment strategies for this disease.

## Key facts

- **NIH application ID:** 10914139
- **Project number:** 5P01HL158505-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Leslie S Kean
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,998
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914139

## Citation

> US National Institutes of Health, RePORTER application 10914139, Defining the T Cell Mediators of Clinical Response in Chronic GVHD (5P01HL158505-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10914139. Licensed CC0.

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