# Project 1: Promoting Graft-versus-Tumor Effects in the Bone Marrow

> **NIH NIH P01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $377,415

## Abstract

PROJECT SUMMARY / ABSTRACT – Project 1
The use of non-myeloablative (NMA) conditioning has allowed curative allogeneic stem cell transplantation
(alloSCT) of older patients (>60yrs) and those with co-morbidities that would otherwise be ineligible for this
approach. The Fred Hutchinson Cancer Research Center and this program grant have pioneered this practice
changing approach over the last 20 years and it has been taken up globally. While we have continued to make
important improvements in supportive care that minimize graft-versus host disease (GVHD) and infectious
mortality, relapse remains a major limitation. This program/project addresses this issue and proposes new
approaches that focus on 1) the use of hematopoietic and plasma cell target antibodies radiolabeled with the
alpha-emitter astatine-211 (211At) to enhance disease eradication during conditioning and 2) mechanisms to
enhance immune-mediated Graft-versus-Leukemia (GVL) in settings where GVHD has been effectively
mitigated. We will utilize novel preclinical models of primary acute leukemia and myeloma to study the effects of
211At-antibody conjugates on GVHD and GVL/ Graft-versus-Myeloma (GVM) after alloSCT. Subsequently we will
test approaches to prevent GVHD that are unlikely to negate GVL, and use this platform to enhance GVL in bone
marrow, using clinically tractable checkpoint inhibitors, deletion of suppressive myeloid cells and/or costimulatory
agonists. Subsequently we will utilize sophisticated protein and transcriptional based approaches to examine the
relationship of T cell function in the peri-transplant period to subsequent survival and disease control in well-
annotated clinical cohorts within Projects 2 and 3. A major focus will be the optimization of innovative
immunotherapy approaches in preclinical systems for clinical translation.

## Key facts

- **NIH application ID:** 10025199
- **Project number:** 2P01CA078902-22
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Geoffrey Roger HILL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,415
- **Award type:** 2
- **Project period:** 1999-04-12 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025199

## Citation

> US National Institutes of Health, RePORTER application 10025199, Project 1: Promoting Graft-versus-Tumor Effects in the Bone Marrow (2P01CA078902-22). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10025199. Licensed CC0.

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