# Engineering CAR-T for treatment of alcoholic liver disease

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $235,125

## Abstract

Summary
Advances in redirecting T cells to attack user-specified target cells using engineered chimeric
antigen receptors (CAR-T) have led to the development of powerful cell-based therapeutics.
Cellular immunotherapies possess several important advantages over traditional small molecule
or antibody-based therapeutics, including the capacity to operate logically through integration of
multiple signals, deliver customized therapeutic payloads, and activate or deactivate through
engineered control.
Here, we propose to adapt and exploit CAR-T technology as a therapeutic strategy in the setting
of alcoholic liver disease (ALD). The forward engineering approach presented here leverages
the principles of synthetic immunology to design, construct and test in vivo next-generation
synNOTCH CAR-T, which are logically activated only in the presence of dual antigens displayed
on the surface of Kupffer cells (KC), the liver resident macrophages. KC represent an excellent
target cell population because of their pivotal role in driving liver inflammation, fibrosis and ALD
progression to irreversible, end-stage cirrhosis and hepatocellular carcinoma.
In Aim 2, we will evaluate the feasibility of utilizing the engineered CAR-T cells developed in Aim
1 to target and eliminate activated KC in vivo, using well established mouse models of alcoholic
liver disease. We will interrogate whether our CAR-T can attenuate ALD disease progression,
block fibrosis and steatosis, and restore liver function.
We anticipate that these studies will establish the feasibility for the application of engineered
CAR-T targeting KC as an effective therapeutic strategy for the treatment of alcoholic liver
disease.

## Key facts

- **NIH application ID:** 10019444
- **Project number:** 5R21AA027535-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DOUGLAS Edmund FELDMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,125
- **Award type:** 5
- **Project period:** 2019-09-20 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019444

## Citation

> US National Institutes of Health, RePORTER application 10019444, Engineering CAR-T for treatment of alcoholic liver disease (5R21AA027535-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10019444. Licensed CC0.

---

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