# Off-the-Shelf Engineered Cord Blood NK Cells for the Treatment of Hematologic Malignancies.

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2022 · $493,218

## Abstract

ABSTRACT / SUMMARY
Despite reports of the strong killing function of NK cells more than four decades ago, adoptive therapy
strategies to exploit this property against late-stage cancer cells have had limited success in the clinic. A major
obstacle to translation has been the lack of reliable methods to enhance the inadequate persistence and
reduced activity of NK cells after their infusion into patients. Thus, the long-term goal of Project 3 is to devise
novel adoptive cell-based therapies for advanced B-lymphoid malignancies (such as acute lymphoblastic
leukemia, chronic lymphocytic leukemia and non-Hodgkin lymphoma). The central hypothesis is: (i) the killing
function of cord blood (CB)-derived NK cells against hematologic cancers can be substantially enhanced with
minimal adverse toxicity, including graft-vs.-host disease, by genetically modifying the cells to express a CD19-
specific chimeric antigen receptor (CAR), a suicide gene (inducible caspase-9, or iC9) and the IL-15 cytokine
to support NK cell proliferation and durability; and ( ii ) it may be feasible to boost this activity by inhibiting the
CISH gene, thus abolishing a pivotal cytokine signaling checkpoint in NK cells and making it possible to
consider the use of lower doses of cell therapy without loss of efficacy. This combined strategy, based on our
recent preliminary findings as well as the transformative successes with CAR.CD19-redirected T cells, will be
pursued in three specific aims. In Aim 1, a first-in-human phase I/II clinical trial, we will evaluate the safety and
antitumor activity iC9/CAR.19/IL15-transduced CB-NK cells in 36 patients with advanced leukemia or
lymphoma. Aim 2 seeks to track the in vivo fate of the transduced cells described above and correlate the
findings with disease responses recorded in Aim 1. This approach will enable us to address several
fundamental issues that have been persistent barriers to more effective modes of adoptive NK cell therapy for
patients with cancer. Finally, Aim 3 will target CIS, a cytokine signaling checkpoint in NK cells, to further
improve the therapeutic potential of our strategy. If we succeed in avoiding toxicity (cytokine release
syndrome, for example) that may be associated with targeted therapies of this type, our project will mark a
clear advance in the development of novel cellular treatments for cancer.

## Key facts

- **NIH application ID:** 10478148
- **Project number:** 5P01CA148600-11
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Katy Rezvani
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $493,218
- **Award type:** 5
- **Project period:** 2011-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10478148

## Citation

> US National Institutes of Health, RePORTER application 10478148, Off-the-Shelf Engineered Cord Blood NK Cells for the Treatment of Hematologic Malignancies. (5P01CA148600-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10478148. Licensed CC0.

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