# Preventing GVHD by inhibition of alloantigen presentation in the gut

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $839,267

## Abstract

PROJECT SUMMARY/ABSTRACT
Blood cancers account for approximately 10% of all malignancies. In addition, non-malignant bone marrow failure
diseases such as aplastic anaemia, or immunodeficiency diseases such as severe combined immunodeficiency,
are life-threatening diseases and allogeneic bone marrow transplantation (BMT) is a preferred curative therapy
for these serious conditions. BMT outcomes are limited by transplant related complications, mainly graft-versus-
host disease (GVHD) and opportunistic infections. Indeed, 15-20% of BMT patients will develop severe GVHD
that is fatal, particularly when involving the GI tract. Current prevention and treatment of GVHD rely on the broad
suppression of T cells and remains suboptimal. The initiation and maintenance of T cell responses are dependent
on activities mediated by antigen-presenting cells (APC) but the types of APC that initiate GVHD and the factors
that promote their function is currently limited. This is the focus of this proposal. In particular, we will build on our
preliminary data to test the hypothesis that epithelial APC in the ileum initiate lethal Th1 dependent acute GVHD.
We will utilize cutting-edge mechanistic preclinical murine studies with parallel clinical analysis, using advanced
flow cytometry, single cell RNA/CITE-seq and ATAC-seq with new spatial protein and sequencing platforms to
focus on antigen presentation in the gastrointestinal tract, identifying clinically tractable pathways that will prevent
the development of lethal acute GVHD. This R01 renewal will continue to identify new, rapidly testing therapeutic
approaches to prevent GVHD based on the inhibition of disease initiation (i.e. alloantigen presentation) rather
than broad T cell suppression in the late effector phase of disease, as is current practice.

## Key facts

- **NIH application ID:** 10893474
- **Project number:** 5R01HL148164-07
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Geoffrey Roger HILL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $839,267
- **Award type:** 5
- **Project period:** 2019-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893474

## Citation

> US National Institutes of Health, RePORTER application 10893474, Preventing GVHD by inhibition of alloantigen presentation in the gut (5R01HL148164-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893474. Licensed CC0.

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