# Memory-like NK cells for enhanced immunotherapy of post transplant relapse in patients with myeloid malignancies

> **NIH NIH R21** · DANA-FARBER CANCER INST · 2021 · $248,243

## Abstract

Project Summary/Abstract
Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN) are
the most common myeloid malignancies in adult patient population. Stem cell transplantation remains the most
curative option as only a fraction of these patients is cured with standard chemotherapy regimens. Recent
advances using post-transplant cyclophosphamide (PTCy) pioneered by researchers at John’s Hopkins
University have significantly improved outcomes after HLA haploidentical donor transplantation (haplo-HCT),
expanding donor availability for patients who otherwise lack traditionally matched donors. However, relapse is
the most common cause of treatment failure after stem cell transplantation including in haplo-HCT patients.
Furthermore, post-transplant relapsed patients have extremely poor prognosis with the current treatment
approaches including donor lymphocyte infusion (DLI); novel therapies are a major unmet need. We and
others recently described cytokine induced memory-like (CIML) NK cells with superior activity against
leukemia cells. CIML NK cells were safe and demonstrated very promising activity (>50% compete remission
rates) in our recently completed early phase trial in patients with advanced AML and MDS in a non-transplant
setting. In the current study we will attempt to harness enhanced anti-leukemia activity of CIML NK cells to
treat patients who have relapsed after haplo-HCT and where donor-derived immunologic environment permits
extended activity and survival of infused cells. In Specific Aim 1, we will assess safety and possible efficacy of
CIML NK cells in patients with myeloid malignancies relapsed after haplo-HCT. Peripheral blood mononuclear
cells will be harvested from the original stem cell donors using non-mobilized leukapheresis and NK cells
separated using two step CD3 depletion followed by CD56 positive selection. CIML NK cells will be generated
from the conventional NK cells by overnight activation with cytokines (IL-12/IL-15/IL-18) and infused into the
patients after they receive lymphodepleting Flu/Cy chemotherapy. Afterwards, the patients will receive low
dose IL-2 (1 x106 IU/m2 SQ every other day x7 doses) to further help support / activate adoptively transferred
CIML NK cells in vivo. In Specific Aim 2, we will sample peripheral blood (PB) and bone marrow (BM) to
characterize immune subsets in detail, track the persistence and functional status of transferred CIML cells and
evaluate the tumor immune microenvironment at the single cell resolution. The proposal incorporates strong
preliminary data, compelling biologic rationale, clinical feasibility, and major therapeutic impact. The results
from this study will potentially help develop a new safer viable treatment option for patients with post-transplant
relapsed myeloid malignancies and help advance our knowledge regarding key aspects of the in vivo CIML NK
cell biology.

## Key facts

- **NIH application ID:** 10075889
- **Project number:** 5R21CA245413-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Rizwan Romee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $248,243
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075889

## Citation

> US National Institutes of Health, RePORTER application 10075889, Memory-like NK cells for enhanced immunotherapy of post transplant relapse in patients with myeloid malignancies (5R21CA245413-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10075889. Licensed CC0.

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