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Ultrasound-controlled remote activation of CAR T cells for localized tumor immunotherapy

Award Number: R01EB029122
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Ultrasound-controlled remote activation of CAR T cells for localized tumor immunotherapy - Ultrasound-Controlled Remote activation of CAR T-cells for localized tumor immunotherapy Chimeric antigen receptor (CAR) T cells show potential as paradigm-shifting therapeutic agents for cancer treatment. CAR-T based immunotherapy, however, can have off-target activity against normal cells and cause life-threatening adverse reactions such as cytokine storms. To mitigate this side effect, we propose to explore high-precision focused ultrasound as a means to confine CAR T cell activation within solid tumor tissue space. In the proposed work, we will use ultrasound to deliver energy safely and noninvasively into small volumes of tissue deep inside the body. We will develop technology and protocols for ultrasound-guided remote-activation of CAR expression in T-cells, which are clinically compatible and able to convert ultrasound waves into short pulses of local heat generation. Specifically, we will engineer molecular thermo-sensors (acousto-sensors) into T-cells along with genetic transducing modules (GTMs), and use focused ultrasound to produce short pulsed heat to activated CAR therapeutic response for focal targeting on solid tumors. We will incorporate reporters to provide direct detection of therapeutic responses, and use the information to calibrate and optimize the system. Therefore, three specific aims are proposed: (1) Develop ultrasound-activatable thermo-sensors and GTMs; (2) Engineer ultrasound-activatable CAR T-cells; (3) Examine the immunotherapeutic efficacy CAR T-cells against solid tumors in vivo. Upon success, this first-of-kind research will specifically transduce remote ultrasound stimulation into genetic expression of T-cells for locally controlled immunotherapy. This approach to solid tumor immunotherapy is expected to open new opportunities to integrate engineering with medicine, and result in many successful translations from fundamental science and engineering to applications with clinical utility.


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	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	10/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$135,992
2024	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	10/12/2023	NON-COMPETING CONTINUATION	-$135,992
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $452,295 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$452,295
2023	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $452,295

Issue Date FY: 2022 ( Subtotal = $463,781 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/7/2022	NON-COMPETING CONTINUATION	$463,781
														Subtotal = $463,781

Issue Date FY: 2021 ( Subtotal = $395,733 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	7/7/2021	NON-COMPETING CONTINUATION	$395,733
														Subtotal = $395,733

Issue Date FY: 2020 ( Subtotal = $411,946 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/15/2020	NEW	$411,946
														Subtotal = $411,946

Grand Total All Awards = $1,723,755

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Ultrasound-controlled remote activation of CAR T cells for localized tumor immunotherapy

Award Number: R01EB029122

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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