# Cord Blood T Cell Therapy for Myeloid Malignancies

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $355,822

## Abstract

PROJECT SUMMARY
Acute myeloid leukemia (AML) is susceptible to immunotherapy as evidenced by the success of allogeneic
(allo) stem cell transplantation (SCT) in this disease. Although allo-SCT can be curative in leukemia, it carries a
high rate of treatment-related mortality and morbidity. This is primarily a result of off-target immune responses
elicited by donor-derived cytotoxic T cells (CTL) within the SCT graft against normal tissues, a phenomenon
known as graft-versus-host disease (GvHD), which occurs in up to 50% of patients following allo-SCT.
Furthermore, AML relapse remains the leading cause of mortality following allo-SCT, highlighting the shortfalls
of allo-SCT in providing long-lasting cures. In order to minimize GvHD, while taking advantage of the graft
versus leukemia (GvL) effect, numerous leukemia-associated antigens (LAAs) have been identified and shown
to elicit leukemia-specific immune responses. PR1 is an HLA-A2-restricted LAA that we identified in our lab
and targeted using a monoclonal T cell receptor (TCR)-like antibody (8F4), a PR1-peptide vaccine, and PR1-
CTL. In the current proposal, we plan to engineer chimeric antigen receptor (CAR) T cells that target PR1/HLA-
A2 on the surface of AML using the 8F4 construct. The rationale for this proposal is that in view of the
shortcomings and significant toxicities associated with allo-SCT, balanced by the susceptibility of AML to
immunotherapy (i.e. allo-SCT), there is a critical need to develop novel immunotherapies to achieve disease
elimination with minimal off-target toxicity. We plan to use 8F4 as the CAR since it has a very high affinity for
the PR1/HLAA2 epitope presented by AML. We plan to use cord blood T cells as the cell source for
engineering the 8F4-CAR T cells due to the success we have recently encountered in engineering and
expanding sufficient numbers of effective 8F4-CAR T cells using cord blood products. Furthermore, we showed
potency of the cord blood-derived 8F4-CAR-T cells in treating human AML in a mouse xenograft model. We
will also introduce a caspase 9 (iCP9) suicide gene into the CAR construct, to increase the safety profile of the
8F4-CAR-T cells. Our central hypothesis is that immunotherapy with iCP9-8F4-CAR T cells engineered from
cord blood T cells will eliminate PR1-expressing AML, with minimal off-target toxicity. We will (1) validate the
safety and anti-leukemic activity of the iCP9-8F4-CAR-T cells in animal models using primary patient AML
samples and cell lines; (2) test the safety and efficacy of the iCP9-8F4-CAR-T cells in patients with AML as a
bridge to allo-SCT; and (3) study immune reconstitution and perform correlative studies using blood and bone
marrow samples from iCP9-8F4-CAR-T cell recipients. After completion of our proposed studies, we anticipate
that PR1-targeting adoptive cellular therapy using 8F4-CAR-T cells could become a standard therapy for
patients with myeloid leukemia. In addition, our studies will elucidate the potent...

## Key facts

- **NIH application ID:** 10247038
- **Project number:** 5P01CA148600-10
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** JEFFREY J MOLLDREM
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $355,822
- **Award type:** 5
- **Project period:** 2011-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247038

## Citation

> US National Institutes of Health, RePORTER application 10247038, Cord Blood T Cell Therapy for Myeloid Malignancies (5P01CA148600-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10247038. Licensed CC0.

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