# Improving the activity of CAR T cells for acute myeloid leukemia

> **NIH NIH K08** · WASHINGTON UNIVERSITY · 2024 · $248,962

## Abstract

Project Summary
Acute myeloid leukemia (AML) has thus far proven resistant to T cell redirecting therapies such as bispecific
antibodies or chimeric antigen receptor (CAR) T cells, which is unexpected given the proven success of these
in other hematologic malignancies. Preliminary studies show that the anti-tumor activity of CD19-targeting CAR
T cells (CART19) is enhanced in the presence of myeloid cells, and that targeting these myeloid cells with
CD33-targeting CART cells (CART33) leads to diminished long-term anti-tumor effect. Furthermore, removing
CD33 from normal myeloid cells improves CART33 expansion and disease control. Based on these findings,
the central hypothesis of this proposal is that bystander myeloid cells enhance CART cell activity, and directly
targeting myeloid cells compromises this effect. The objective of this proposal is to delineate how myeloid cells
influence CAR T cell behavior when they are targets of therapy, as compared to when they are simply
bystanders, so that we can intervene within these interactions and improve CAR T cell therapy for AML. This
will be achieved through the following specific aims: 1) Determine how bystander myeloid cells modulate CAR
T cell function; 2) Determine how targeting myeloid cells changes CAR T cell profile. To this end,
hematopoietic stem cells (HSCs) will be engineered through either viral gene transfer or CRISPR/Cas9 gene
knockout to generate myeloid cells that are positive or negative for the antigen targeted by the CAR. The
effects of wild-type or genetically modified myeloid cells on CAR T cells will be interrogated by in vitro culture
and in vivo mouse models, using flow cytometry, single-cell RNA-seq, and functional studies. The innovations
of this project are that it draws attention to host environmental factors that influence CAR T cell activity, and
advances the concept that the nature of the cell being targeted can influence CAR T cell behavior. This
research is significant because it will contribute to a better understanding of how CAR T cells work with the
immune environment, and illuminate methods to intervene within these interactions to improve the outcomes of
therapy. The long-term goal of this proposal is to establish the applicant Dr. Miriam Kim's career as an
independent researcher focused on developing novel cell therapies for AML. The proposed research and
career development plan will provide Dr. Kim with training in HSC/myeloid biology, immunology, and
bioinformatics. Her primary mentor, Dr. John DiPersio, and co-mentors Drs. Robert Schreiber, Todd Fehniger
and Carl DeSelm, offer complementary expertise in cell engineering and immunotherapy. Additionally, Dr.
Kim's collaborators Dr. Li Ding and Dr. Feng Gao will contribute to developing her skills in bioinforrnatics and
biostatistics. Furthermore, Washington University provides an ideal environment for Dr. Kim to successfully
establish herself as an independent investigator.

## Key facts

- **NIH application ID:** 10876996
- **Project number:** 5K08CA277000-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Miriam Y Kim
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,962
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876996

## Citation

> US National Institutes of Health, RePORTER application 10876996, Improving the activity of CAR T cells for acute myeloid leukemia (5K08CA277000-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10876996. Licensed CC0.

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