# BM NICHE DISRUPTION AND IMMUNOTHERAPY IN HEMATOLOGICAL MALIGNANCIES

> **NIH NIH R50** · WASHINGTON UNIVERSITY · 2020 · $175,922

## Abstract

Abstract
Hematopoietic stem cell transplant (HSCT) remains the only curative therapy for many patients with
hematologic malignancies and marrow failure states. Key obstacles to the success of HSCT include collecting
optimal numbers of hematopoietic stem cells capable of multilineage and durable engraftment, control of graft-
versus-host disease (GvHD) and treating disease recurrence both before and especially after HSCT. Dr.
DiPersio has focused his career over the last 20 years on overcoming these three obstacles to HSCT through
the use of a bench-to-bedside and back again research approach. I have been fortunate to spend my entire
15-year post-graduate research career working with Dr. DiPersio. During this time, I have contributed to 16 of
Dr. DiPersio's peer-reviewed manuscripts, completed pre-clinical studies for 4 projects that led to first-in-
human clinical trials, assisted in the training of 9 post-docs and/or fellows, trained and supervised 4 technicians
and performed correlative studies for 17 different clinical trials involving over 400 patients. Dr. DiPersio's
research program over the next several years will use our strengths in preclinical modeling, cancer genomics
and the design and execution of early phase clinical trials to 1) develop novel and highly clinically relevant
methods to target the hematopoietic niche for optimal mobilization of hematopoietic stem cells and chemo- and
nanoparticle-sensitization of acute myeloid leukemia (AML) and multiple myeloma; 2) characterize the genetic
and epigenetic changes that contribute to AML relapse after allogeneic hematopoietic stem cell transplantation
(alloHSCT); and 3) design and test novel AML immunotherapeutics to reduce the risk of AML relapse before or
after HSCT. Successful HSCT requires the infusion of a sufficient number of hematopoietic stem cells that are
capable of homing to the bone marrow cavity and regenerating durable trilineage hematopoiesis in a timely
fashion. In our first research area, we will use multiple strategies to enhance stem cell mobilization and
leukemia chemo- and nanoparticle-sensitization via targeted modulation of the CXCR4/CXCL12, VLA-
4/VCAM-1 and CXCR2/CXCL1-7 axes. In our second major research area we will identify the genetic changes
that contribute to AML relapse after alloHSCT in man and mice. Finally, since most patients with AML die from
progressive disease after relapse, our third research area will develop and translate into early phase clinical
trials novel bi- and tri-specific monoclonal antibody reagents for the treatment of AML relapse before and after
HSCT. We will complete a “first-in-man” phase I clinical trial of MGD006, a CD123×CD3 Dual Affinity Re-
Targeting (DART) bispecific antibody-based molecule, in patients with relapsed/refractory AML. While this trial
is ongoing we are identifying novel targets for immunotherapy in AML and testing the efficacy of new
retargeting agents that engage either T cells, NK cells or other immune effec...

## Key facts

- **NIH application ID:** 9994843
- **Project number:** 5R50CA211466-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Michael Rettig
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $175,922
- **Award type:** 5
- **Project period:** 2016-09-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9994843

## Citation

> US National Institutes of Health, RePORTER application 9994843, BM NICHE DISRUPTION AND IMMUNOTHERAPY IN HEMATOLOGICAL MALIGNANCIES (5R50CA211466-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9994843. Licensed CC0.

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