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

Award Number: R21EB029614
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/15/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2024

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	8/19/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	3/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $201,875 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	8/3/2022	NON-COMPETING CONTINUATION	$20,188
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	1/19/2022	NON-COMPETING CONTINUATION	$181,687
														Subtotal = $201,875

Issue Date FY: 2021 ( Subtotal = $201,875 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	6/1/2021	NON-COMPETING CONTINUATION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	3/19/2021	NON-COMPETING CONTINUATION	$201,875
														Subtotal = $201,875

Issue Date FY: 2020 ( Subtotal = $241,876 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	4/9/2020	NEW	$241,876
														Subtotal = $241,876

Grand Total All Awards = $645,626

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

Award Number: R21EB029614

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/15/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2024

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