# Project 2: Towards a safe and effective AML treatment strategy using anti-CD33 CAR T cells in combination with CAR-resistant hematopoietic stem cells

> **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $317,421

## Abstract

SUMMARY/ABSTRACT (PROJECT 2) 
Immunotherapy has revolutionized the treatment of a variety of advanced malignancies. Anti-CD19 chimeric 
antigen receptor redirected T cells (CART-19) have been particularly successful in B-cell malignancies. How to 
translate the success of CART cell therapy to other malignancies such as acute myeloid leukemia (AML) 
remains an important question in the field. A critical requirement of CART cell therapy is that the target tissue 
be expendable. AML is a malignancy of the hematopoietic stem/progenitor cells (HSPC) and shares cell 
surface antigens with normal HSPC and with normal myeloid progeny such as neutrophils and monocytes. It 
has become clear that the lack of AML-specific antigens is the single biggest impediment to unleashing the 
power of CART cells against AML and other myeloid malignancies. The long-term goal of this project is to 
develop a clinically feasible CART cell platform for AML, by creating AML-specific CART cells that are able to 
expand and persist in vivo to eradicate AML while preserving normal marrow function. The central hypothesis 
is that a durable anti-leukemic effect from anti-CD33 CART cells can co-exist with adequate levels of 
genetically engineered CD33-deficient hematopoiesis. This will be accomplished in three specific aims. In Aim 
1, high quality depletable anti-CD33 CAR T cells will be manufactured. These will be allogeneic, donor-derived 
T cells transduced with a biscistronic lentiviral vector that encodes a humanized anti-CD33-41BB-zeta CAR as 
well as CD20. In Aim 2, the feasibility and safety of manufacturing CD33-deficient human HSPC will be tested 
and regulatory approvals to manufacture CD33-deficient HSPC will be obtained. In Aim 3, a clinical trial will be 
conducted of a combined approach incorporating CD33-deficient, CAR-resistant allogeneic HCT followed by 
CART-33 infusion in patients with AML. This research will be significant because it will contribute depth (of 
clinical responses) and breadth (of eligibility for potentially curative therapy) to the therapeutic arsenal against 
AML. The innovation of the proposed research lies in replacing the search for suitable leukemia-specific 
antigens with a novel platform that combines pan-myeloid specific CART (such as CART-33) with an infusion 
of donor HSPC that are genetically engineered to lack CD33 and which are therefore resistant to killing by 
CART-33.

## Key facts

- **NIH application ID:** 10245064
- **Project number:** 5P01CA214278-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** CARL H. JUNE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $317,421
- **Award type:** 5
- **Project period:** 2017-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10245064

## Citation

> US National Institutes of Health, RePORTER application 10245064, Project 2: Towards a safe and effective AML treatment strategy using anti-CD33 CAR T cells in combination with CAR-resistant hematopoietic stem cells (5P01CA214278-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10245064. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*