# Specific Adoptive Immunotherapy of AML with Engineered CD8+ T Cells

> **NIH NIH P01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2021 · $904,588

## Abstract

Project Summary/Abstract
Project 1
The outcome for patients diagnosed with AML remains poor, especially for patients older than 60. The quality
of remission achieved with induction therapy is a major predictor of outcomes, and ~90% of patients with
detectable minimal residual disease (MRD) or incomplete platelet (CRp) or peripheral count recovery (CRi)
after induction will relapse in the 1st year regardless of consolidation therapies. Although allogeneic
hematopoietic cell transplant (HCT) is recommended for these patients, ~1/3 are either not candidates or
choose to not have an HCT. Adoptive T cell therapy offers a novel strategy to selectively target leukemic cells
with limited toxicity to the patient. We previously demonstrated AML could be therapeutically targeted with
WT1-specific CD8 T cells, and, in the last grant cycle, showed that relapse of AML in high risk patients
post-HCT could be prevented by infusion of donor CD8 T cells engineered to express a high affinity
WT1-specific TCR. We now propose to advance this T cell therapy to non-HCT patients. This setting allows us
to address many critical questions not feasible in post-HCT patients about the requirements for efficacy and
the obstacles to success, including the importance of the type of CD8 T cell engineered, and the contribution of
lympho-depletion to cell persistence/activity. The long-term goal is to develop a reproducibly effective T cell
therapy regimen for AML that can be deployed in non-HCT as well as HCT patients. The aims are:
1. Evaluate in a Phase I/II trial the safety and potential efficacy of transduced autologous CD8+ naïve (TN),
central memory (TCM), or EBV-specific (TEBV) T cells expressing a high affinity TCR specific for WT1 infused
after induction/consolidation in patients in morphologic CR but with MRD, Cri, or CRp after induction therapy.
2. Determine if transduced cells derived from autologous CD8+ TN, TCM, or TEBV cells have distinct abilities to
persist, localize to bone marrow (BM), retain function, and/or potentially eradicate leukemic cells after in vitro
expansion and in vivo transfer. Endogenous TCR gene sequences will be used to barcode the transduced cells
to make it possible to distinguish the contribution of each subset in vivo in the same patient.
3. Identify biologic parameters associated with treatment success or failure, including features of the leukemia
and the T cells, and gain insights into strategies to overcome treatment obstacles. Leukemia cells will be
evaluated for loss of the WT1 epitope or Class I, changes in antigen processing, and expression of inhibitory
molecules; T cell subsets will be evaluated and compared, including by high throughput single cell PCR, for
functional pathways, exhaustion, and molecular changes that influence biologic activity.

## Key facts

- **NIH application ID:** 10143195
- **Project number:** 5P01CA018029-45
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** PHILIP D GREENBERG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $904,588
- **Award type:** 5
- **Project period:** 1997-08-28 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143195

## Citation

> US National Institutes of Health, RePORTER application 10143195, Specific Adoptive Immunotherapy of AML with Engineered CD8+ T Cells (5P01CA018029-45). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10143195. Licensed CC0.

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