# Optimizing Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Malignancies

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2022 · $204,944

## Abstract

Project Summary/Abstract
 This NCI Diversity Supplement application outlines the research and career development plans for
Stephen Persaud, M.D., Ph.D, who is preparing for a career as an academic physician-scientist. Dr. Persaud
completed his M.D. and PhD in immunology in 2015 at Washington University School of Medicine, then
completed his residency in Clinical Pathology in 2018 at Barnes-Jewish Hospital as part of the Physician
Scientist Training Program. During his residency elective time, he began his postdoctoral research in the lab of
John DiPersio, M.D., Ph.D, Chief of the Oncology Division in the Department of Medicine at Washington
University School of Medicine. Dr. DiPersio is an expert in allogeneic hematopoietic stem cell transplantation
(allo-HSCT), normal and malignant hematopoiesis, and cellular immunotherapy, and has an outstanding track
record of training successful physician-scientists. The scientific resources and environment provided by the
DiPersio lab and Washington University School of Medicine, combined with the mentoring, educational, and
training plans described herein, will propel Dr. Persaud’s career forward by enhancing the growth of his
independent research program and his competitiveness for extramural funding.
 The long-term goal of the proposed research is to optimize minimally toxic, antibody-based
HSCT conditioning regimens for the therapy of acute myeloid leukemia (AML). Led by Dr. Persaud, the
DiPersio lab published the first study showing that CD45- or cKit-targeted antibody-drug conjugates (ADCs)
combined with Janus kinase 1/2 (JAK1/2) inhibitors enabled fully MHC-mismatched HSCT in mice, with
myeloid donor chimerism ≥99%. Notably, unlike conditioning with irradiation, ADC-based conditioning did not
promote graft-versus-host disease (GvHD). Finally, JAK1/2 inhibitors plus CD45-ADC balanced GvHD with
GvL activity in a delayed donor lymphocyte infusion lymphoma model, with evidence of direct ADC-mediated
antitumor efficacy. By enabling allogeneic engraftment and GvL effects while mitigating GvHD and systemic
toxicities, our novel regimen provides the ideal blend of activities for the immediate post-transplant period in
the treatment of AML. We will build on this body of work with two Specific Aims. In Aim 1, we will develop and
characterize fully myeloablative CD45 and cKit ADCs and evaluate their antileukemic efficacy and impact on
GvHD and GvL responses. In Aim 2, we will develop toxic payload-free, antibody-based conditioning methods
by combining anti-cKit and anti-CD47 targeting with JAK1/2 inhibition, which we hypothesize will
simultaneously condition for allo-HSCT and eliminate leukemia cells. Collectively, these studies will adapt
antibody-based conditioning strategies for the purpose of treating hematologic malignancies, achieving
maximal antileukemia benefit with minimal injury to the host.

## Key facts

- **NIH application ID:** 10596338
- **Project number:** 3R35CA210084-06S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** John F. Dipersio
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,944
- **Award type:** 3
- **Project period:** 2017-09-07 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596338

## Citation

> US National Institutes of Health, RePORTER application 10596338, Optimizing Hematopoietic Stem Cell Transplantation for the Treatment of Hematological Malignancies (3R35CA210084-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10596338. Licensed CC0.

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