# Chimeric Antigen Receptor (CAR) Directed T-regulatory Cell Therapy for Aortic Aneurysm

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $201,875

## Abstract

Project Summary/Abstract
The objective of the proposed research is to develop a precision T-regulatory cell (Treg)-based treatment to
prevent growth and rupture of abdominal aortic aneurysms (AAA), a leading cause of death in developed
countries. AAA result from uncontrolled inflammation.Thus, modulation of aortic specific inflammation could
lead to the development of medical treatment for AAA, thereby delaying or preventing the need for surgical
intervention and ultimately removing the risk of aneurysm-related death.
Tregs are vital in preventing autoimmune diseases and promoting resolution of immune response. Recently,
Chimeric Antigen Receptors (CARs) have been used to generate precision therapy by directing T-cells to bind
and activate at specific locations within the body. We therefore hypothesize that we can engineer a CAR to be
expressed in Tregs that will direct them to bind to damaged aortic tissue and block the inflammatory process.
Elastin Binding Protein (EBP) is an endogenous receptor that directs inflammatory cells to damaged aortic
tissue in humans. Consequently, EBP is an ideal candidate to direct Tregs to damaged aortic tissue in AAA
patients as a key component of a CAR. Our team has significant experience studying vascular inflammation,
AAA, and Treg biology, and has successfully engineered CARs in the past. Based on our collective expertise
we propose to investigate two Specific Aims to characterize the interaction of Tregs and damaged aortic tissue
and generate an engineered Treg to be used to treat AAA: Aim 1: Genetically modify Tregs to express an EBP-
CAR that targets damaged elastin in aortic tissue. Aim 2: Evaluate the binding capacity and activation of Tregs
and genetically modified Tregs to aortic tissue from patients with aortic aneurysms.
We believe these studies will allow us to gain a more in-depth understanding of the interaction between Tregs
and damaged aortic tissue, while developing an innovative strategy to oppose vascular inflammation. If
successful, this work will allow us to generate a CAR-Treg that can be tested for efficacy in animal models of
AAA and potentially be translated into a novel therapeutic tool for the treatment of AAA, a disease that
currently lacks effective medical treatment options.
!
!

## Key facts

- **NIH application ID:** 10375495
- **Project number:** 5R21EB029614-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Adam Oskowitz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2020-04-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375495

## Citation

> US National Institutes of Health, RePORTER application 10375495, Chimeric Antigen Receptor (CAR) Directed T-regulatory Cell Therapy for Aortic Aneurysm (5R21EB029614-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375495. Licensed CC0.

---

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