# Project 5 - Memory-like NK cell augmented hematopoietic cell transplantation for AML.

> **NIH NIH P50** · WASHINGTON UNIVERSITY · 2020 · $326,161

## Abstract

Project Summary/Abstract
The long-term goals of this project are to translate novel findings in the field of immunology into early phase
immunotherapy clinical trials for patients with leukemia. Allogeneic hematopoietic cell transplantation (HCT) is
a standard treatment for high-risk or relapsed AML and is potentially curative. However, major barriers to
success in older AML patients include 1) an inability to tolerate intensive conditioning, 2) disease relapse, 3)
graft-versus-host disease (GVHD), and 4) the lack of a suitable donor in many cases. One key immune player
in mediating the graft-versus-leukemia (GvL) effect that also potentially limits GVHD is the NK cell. We
hypothesize that new findings in NK cell biology can be translated to the clinic to improve the effectiveness and
tolerability of HCT in older AML patients.
 Recent clinical studies have reported that HCT from an MHC-haploidentical donor (haplo-HCT) with
myeloablative conditioning regimens that incorporate post-HCT cyclophosphamide results in clinical outcomes
that are comparable to HCT from matched unrelated donors. However, one major obstacle to treating AML
patients with haplo-HCT is the large number of older patients that are only candidates for reduced-intensity
conditioning (RIC), which results in lower treatment-related mortality, but at the cost of a much higher incidence
of AML relapse, and thus far, poor long-term disease-free survival. To address this important hurdle in the field,
we will augment HCT with same-donor memory-like NK cell adoptive immunotherapy during the immediate
post-HCT period, to enhance GvL while potentially improving engraftment and minimizing GVHD.
 Reports have recently identified that NK cells exhibit “memory-like” properties following combined cytokine
pre-activation. We and others have established that human memory-like NK cells respond robustly after a
second stimulation and have multiple anti-tumor properties. We have translated this into a cellular therapy for
relapsed/refractory (rel/ref) AML patients, and have completed a phase 1 study. However, one drawback of this
allogeneic NK cell therapy is its rejection by the recipient's recovering immune system after 2-3 weeks,
providing a short “window of opportunity” for these NK cells to eliminate AML. To address this limitation in the
NK immunotherapy field, we will incorporate a donor-matched RIC HCT, providing an ideal immune-compatible
environment for memory-like NK cells to expand and attack residual AML.
 In this proposal, we will 1) test the safety and efficacy of augmenting RIC HCT with same-donor memory-
like NK cell adoptive immunotherapy in a phase 2 clinical trial for patients with AML, 2) define memory-like NK
cell correlates of clinical response, and elucidate key mechanisms important for memory-like NK cell anti-AML
responses. These studies will lead to a new understanding of mechanisms whereby NK cells effectively attack
AML, and whereby AML resists NK cell therapy, and hence...

## Key facts

- **NIH application ID:** 9961541
- **Project number:** 5P50CA171963-08
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** TODD A FEHNIGER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,161
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961541

## Citation

> US National Institutes of Health, RePORTER application 9961541, Project 5 - Memory-like NK cell augmented hematopoietic cell transplantation for AML. (5P50CA171963-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9961541. Licensed CC0.

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