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Precise tumor targeting with logic CAR circuits

Award Number: U01CA265713
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/17/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Precise tumor targeting with logic CAR circuits - Project Summary This proposal describes a unique SUPRA CAR system in human T cells to address in vivo off-tumor toxici- ty, using an established liver transgene expression mouse model. We will use our recently developed split, universal and programmable (SUPRA) CAR system that simultaneously encompasses multiple critical up- grades, such as the ability to finely tune T cell activation strength, sense and logically respond to multiple antigens, and independently regulate two T cell subtypes simultaneously. Specifically, we will evaluate two types of circuits: (1) AND and (2) NIMPLY (A AND NOT B) logic CAR circuits, which have been determined bioinformatically as the best type for circuits for discriminating tumors from healthy cells. The proposed exper- iments will test the hypotheses that (1) our modular and tunable logic CAR T systems are uniquely suited for preventing on-target off-tumor toxicity in vivo, even when healthy tissues expressing a tar- get antigen are near the tumor, and (2) the tumor specificity and activity of our SUPRA CAR systems is enhanced by controlled delivery. Importantly, preliminary data support these hypotheses, and well- characterized materials and rigorous experimental designs are established in this proposal with essential cross-disciplinary collaborations and expertise that encompass synthetic biology, immunology, animal tumor biology, and biomaterials. The specific aims of this five-year proposal are as follows: Aim 1 evaluates AND log- ic SUPRA CAR specificity in vivo. Aim 2 investigate the tumor specificity and toxicity of NIMPLY logic SUPRA CAR in vivo. Aim 3 determine the effect of adaptor protein delivery mechanism on tumor-targeting specificity. Outcomes from this work will establish the clinical potential of logic CAR systems and expand their use to addi- tional cancers, including solid tumors.


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: 2025 ( Subtotal = $323,559 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	5	8/20/2025	NON-COMPETING CONTINUATION	$323,559
														Subtotal = $323,559

Issue Date FY: 2024 ( Subtotal = $525,026 )
2024	2024	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	4	8/9/2024	NON-COMPETING CONTINUATION	$525,026
														Subtotal = $525,026

Issue Date FY: 2023 ( Subtotal = $553,669 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	3	8/3/2023	NON-COMPETING CONTINUATION	$553,669
														Subtotal = $553,669

Issue Date FY: 2022 ( Subtotal = $554,582 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	001	2	8/24/2022	NON-COMPETING CONTINUATION	$554,582
2022	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	1	7/19/2022	NEW	$0
														Subtotal = $554,582

Issue Date FY: 2021 ( Subtotal = $582,303 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	1	9/17/2021	NEW	$582,303
														Subtotal = $582,303

Grand Total All Awards = $2,539,139

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Precise tumor targeting with logic CAR circuits

Award Number: U01CA265713

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/17/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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