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Multi-strain, live biotherapeutics as adjuncts to checkpoint inhibitor therapy

Award Number: R21CA249822
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/17/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Multi-strain, live biotherapeutics as adjuncts to checkpoint inhibitor therapy - PROJECT SUMMARY A series of recent studies have highlighted the importance of the composition of the gut microbiota as a factor determining the efficacy of checkpoint inhibitor therapy to treat a variety of cancers. These studies have identified a number of phylogenetically unrelated taxa that lack consistency across reports, generating confusion and skepticism in the field. We evaluated the effect of prebiotics (inulin and mucin) and found that these treatments induce alterations in gut microbiota composition and lead to tumor growth attenuation in some but not all of the tumor models tested. Comparison of microbiota profiles of mice associated with effective tumor control to those that failed to do so, suggests that bacterial species encoding anti-tumor phenotypes are enriched in a number of distinct phylogenetic clades. Similarly, we observed that anti-tumor taxa are positively correlated with distinct TILs profiles suggesting that an optimized bacterial cocktail capable of stimulating multiple anti-tumor immune responses may allow more robust tumor growth control. We will test whether inulin feeding restores tumor control of gnotobiotic mice colonized with fecal microbiota from patients that were non-responsive to checkpoint inhibitor therapy. We are strongly positioned to engage in translational efforts to target the isolation and validation of relevant phylogenetic groups to identify taxa promoting improved responsiveness to checkpoint inhibitors as an important step toward developing optimized probiotic formulations for use in human patients. We will explore mechanistic aspects of inulin's ability to confer anti-tumor immunity we will conduct metabolomics analyses using gnotobiotic mice colonized with defined, low-complexity communities and in vitro cultures to identify inulin- dependent metabolites that may signal the gut immune system to induce anti-tumor immunity.


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	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	2	1/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $212,696 )
2022	2022	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	2	4/13/2022	NON-COMPETING CONTINUATION	$212,696
														Subtotal = $212,696

Issue Date FY: 2021 ( Subtotal = $263,086 )
2021	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	001	1	5/28/2021	NEW	$0
2021	2021	SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE	10901 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Treatment Research	000	1	5/17/2021	NEW	$263,086
														Subtotal = $263,086

Grand Total All Awards = $475,782

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Multi-strain, live biotherapeutics as adjuncts to checkpoint inhibitor therapy

Award Number: R21CA249822

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/17/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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