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Engineering S. typhimurium for metastatic colorectal cancer

Award Number: R01EB029750
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: 06/15/2020
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Engineering S. typhimurium for metastatic colorectal cancer - The engineering of living cells and microbes is driving a new era of cancer therapy. This transformative approach allows for the genetic programming of living cells to intelligently sense and respond to environments, ultimately adding specificity and efficacy that is otherwise unattainable with molecular-based therapeutics. Due to recent microbiome studies indicating the prevalence of bacteria within the human body and specifically in tumor tissue, bacteria have generated significant interest as cancer therapies. Additionally, a multitude of empirical studies have demonstrated that administered bacteria home and selectively grow in tumors due to reduced immune surveillance of tumor cores. Given their presence and selectivity for tumors, bacteria present a unique oppor- tunity to be engineered as intelligent delivery vehicles for cancer therapy. The objective of this proposal is to engineer and optimize S. typhimurium for metastatic colorectal cancer therapy. Since animal based-testing regimes limit the rate of clinical progress, we will use a high-throughput, bacteria-spheroid platform to rapidly test therapeutic payloads and production and release strategies. We will also assess the effect of therapies on colorectal genetic backgrounds, and investigate spatio-temporal hetero- geneity in 3D spheroids with the use of engineered cell reporters. We will then test lead candidates in mouse models of primary and metastatic colorectal cancer to evaluate safety and efficacy. We will focus on colorectal cancer due to several proof-of-concept studies from our lab demonstrating efficacy in colorectal spheroids and animal models. In particular, we showed that oral delivery of bacteria can specifically colonize colorectal liver metastases, providing an attractive delivery route as a cancer therapy. Since these metastases are often con- fined to the liver, this approach can have a significant impact on tumor growth and survival. The research in this proposal will help to establish a framework to genetically engineer microbes for cancer therapy, and significantly accelerates tools that will impact the broader cancer and synthetic biology communities. If successful, future lead candidates for potential clinical trials will be identified on the basis of therapeutic efficacy and safety studies from this proposal.


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 = $0 )
2025	2024	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	2/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $352,142 )
2024	2024	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	001	4	4/29/2024	NON-COMPETING CONTINUATION	$28,747
2024	2024	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	11/30/2023	NON-COMPETING CONTINUATION	$323,395
														Subtotal = $352,142

Issue Date FY: 2023 ( Subtotal = $357,852 )
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	002	3	3/13/2023	NON-COMPETING CONTINUATION	$0
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	3	11/2/2022	NON-COMPETING CONTINUATION	$322,067
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	001	3	1/31/2023	NON-COMPETING CONTINUATION	$35,785
														Subtotal = $357,852

Issue Date FY: 2022 ( Subtotal = $350,841 )
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	002	2	7/11/2022	NON-COMPETING CONTINUATION	$35,085
2022	2022	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	001	2	11/30/2021	NON-COMPETING CONTINUATION	$315,756
2022	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	10/28/2021	NEW	$0
														Subtotal = $350,841

Issue Date FY: 2021 ( Subtotal = $0 )
2021	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	5/31/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $346,661 )
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	6/11/2020	NEW	$346,661
														Subtotal = $346,661

Grand Total All Awards = $1,407,496

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Engineering S. typhimurium for metastatic colorectal cancer

Award Number: R01EB029750

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: 06/15/2020

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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