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Probiotic guided CAR-T therapy (ProCARs) for breast cancer

Award Number: R01EB030352
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: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2024

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Probiotic guided CAR-T therapy (ProCARs) for breast cancer - PROJECT SUMMARY The engineering of immune cells such as chimeric antigen receptor (CAR)-T cells is driving a new era of cancer therapy. What makes this approach transformative is the ability to genetically program living cells to intelligently sense and respond to environments, adding specificity and efficacy that is not possible to obtain with molecular and antibody-based therapeutics. While CAR-T cell therapy has demonstrated remarkable success for hemato- logical malignancies, it has been faced with many challenges in solid tumor treatment including limitations in targeting safe tumor antigens, poor infiltration into tumors, and increased T cell dysfunction in the suppressive tumor microenvironment. Thus, there is a pressing need to develop technologies to enhance the safety and efficacy of this promising approach for solid tumors. Over the last few decades, microbiome and mechanistic studies have elucidated that bacteria selectively colonize tumor necrotic cores due to reduced immune surveil- lance. Where CAR-T cells struggle to target, locate, and infiltrate solid tumors, bacteria naturally home to, colo- nize, and remain indifferent to the antigenic profile of tumors. Due to advances in engineering capabilities from synthetic biology, microbes represent a natural platform for development as 'smart’ therapeutic delivery vehicles for cancer. In this way, probiotics can infiltrate tumors and be engineered as beacons for directing and enhancing CAR-T cell activities. This project proposal seeks to engineer a bridge between these two complimentary forms of cellular therapies for the treatment of triple negative breast cancer (TNBC). The objective of this proposal is to engineer bacteria and CAR-T cells together, developing a ProCAR (probiotic guided CAR-T cell) system that will improve the limitation of individual agents. Specifically, probiotics will be engineered to home to tumors and locally produce immune-stimulants to enhance CAR-T cell therapies – while CAR-T cells will be engineered to sense these molecules. The overarching innovation of this proposal is engineering communities of living medi- cines, where tumor colonizing bacteria are reengineered as beacons for directing and enhancing CAR-T cell cytotoxicity. This will be a fundamentally new approach to genetically engineering interactions between living medicines, combining the advantages of CAR-T cells and tumor-specific bacteria for cancer therapy, and further building the foundation for engineered communities.


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 = -$6,099 )
2025	2023	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	1/3/2025	NON-COMPETING CONTINUATION	-$6,099
														Subtotal = -$6,099

Issue Date FY: 2023 ( Subtotal = $664,480 )
2023	2023	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	6/29/2023	NON-COMPETING CONTINUATION	$664,480
														Subtotal = $664,480

Issue Date FY: 2022 ( Subtotal = $676,866 )
2022	2022	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	202 LOW LIBRARY 535 W 116 ST MC 4309,	NEW YORK	NY	10027	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	8/10/2022	NON-COMPETING CONTINUATION	$676,866
														Subtotal = $676,866

Issue Date FY: 2021 ( Subtotal = $675,112 )
2021	2021	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	7/7/2021	NON-COMPETING CONTINUATION	$675,112
														Subtotal = $675,112

Issue Date FY: 2020 ( Subtotal = $660,386 )
2020	2020	TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK, THE	116TH AND BDWY	NEW YORK	NY	10027	NEW YORK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	9/15/2020	NEW	$660,386
														Subtotal = $660,386

Grand Total All Awards = $2,670,745

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Probiotic guided CAR-T therapy (ProCARs) for breast cancer

Award Number: R01EB030352

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: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2024

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