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Translation of commensal bacteria mechanism for immunotherapy

Award Number: R01CA245292
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/02/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Translation of commensal bacteria mechanism for immunotherapy - PROJECT SUMMARY Microbiota are associated with remarkable effects on host health and disease. Notably, discrete species of commensal bacteria have been correlated with improved patient responses to cancer immunotherapy. However, the molecular mechanisms underlying the functions of these beneficial bacteria remain poorly understood. In particular, specific strains of Enterococci have been linked with improved response to anti-PD-1/PD-L1 treatment in patients with metastatic melanoma, lung, and kidney cancers, but their mechanism of action has not been elucidated nor employed to improve cancer immunotherapy. Recent work from the Hang laboratory has demonstrated that these beneficial strains of Enterococci have unique peptidoglycan composition and remodeling enzymes. Based on these studies, this project hypothesizes that specific strains of Enterococci may prime innate immune signaling pathways and enhance anti-PD-1/PD-L1 immunotherapy against metastatic cancers. To evaluate the activity and mechanism(s) of Enterococci during immunotherapy as well as co-opt their protective factors for cancer immunotherapy, this proposal will examine how specific Enterococci strains alter cancer growth, immune cell populations, and microbiota composition in mouse models of cancer immunotherapy. In addition, the Hang laboratory will identify Enterococci protective factors and engineer them into existing human probiotics to translate our basic microbiota-cancer immunotherapy findings into novel therapeutic agents. Finally, the Hang laboratory will also synthesize novel immunomodulatory small molecules that activate host pathways used by Enterococci to enhance cancer immunotherapy. These studies will reveal fundamental microbiota- cancer immunotherapy mechanisms and develop new therapeutic strategies and agents to enhance cancer immunotherapy.


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	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	6	4/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $527,560 )
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	6	11/30/2023	NON-COMPETING CONTINUATION	$499,794
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	001	6	4/23/2024	NON-COMPETING CONTINUATION	$27,766
														Subtotal = $527,560

Issue Date FY: 2023 ( Subtotal = $544,219 )
2023	2023	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	001	5	3/15/2023	NON-COMPETING CONTINUATION	$44,425
2023	2023	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	5	12/19/2022	NON-COMPETING CONTINUATION	$499,794
														Subtotal = $544,219

Issue Date FY: 2022 ( Subtotal = $544,219 )
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	001	4	5/17/2022	NON-COMPETING CONTINUATION	$44,426
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	4	12/1/2021	NON-COMPETING CONTINUATION	$499,793
														Subtotal = $544,219

Issue Date FY: 2021 ( Subtotal = $546,030 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	005	3	8/13/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$5,775
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	004	2	8/13/2021	NON-COMPETING CONTINUATION	-$5,775
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	002	2	8/10/2021	NON-COMPETING CONTINUATION	-$333,306
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	2	12/1/2020	NON-COMPETING CONTINUATION	$503,782
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	003	3	8/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$349,038
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	001	2	1/28/2021	NON-COMPETING CONTINUATION	$26,516
														Subtotal = $546,030

Issue Date FY: 2020 ( Subtotal = $530,298 )
2020	2020	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	000	1	12/2/2019	NEW	$517,521
2020	2020	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cancer Treatment Research	001	1	1/24/2020	NEW	$12,777
														Subtotal = $530,298

Grand Total All Awards = $2,692,326

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Translation of commensal bacteria mechanism for immunotherapy

Award Number: R01CA245292

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/02/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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