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Investigating Mechanisms of Adaptive Immune Resistance to Combination Immunotherapy within the Glioblastoma Microenvironment

Award Number: P50CA211015
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/11/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Investigating Mechanisms of Adaptive Immune Resistance to Combination Immunotherapy within the Glioblastoma Microenvironment - PROJECT SUMMARY/ABSTRACT – Overall The objectives of the UCLA SPORE in Brain Cancer are to contribute significantly to progress in the diagnosis, prognosis, and treatment of brain cancer. These goals will be accomplished through multiple and diverse research projects involving mechanistic pre-clinical work and innovative clinical studies, with a particular focus on developing novel strategies to overcome the problem of treatment-induced resistance. The broad, long-term objectives and aims of our brain cancer SPORE are as follows: 1) to investigate mechanisms of immunotherapy-induced immune evasion following active immunotherapy, and develop rational combinations of immunotherapeutic strategies to overcome the immunosuppressive milieu of the brain tumor microenvironment; 2) to elucidate the alterations in cellular metabolism associated with drug- induced resistance to apoptosis, and exploit targeting apoptotic blocks to induce intrinsic tumor cell death; and 3) to explore the concept of radiation-induced phenotype conversion of non-tumorigenic cells to glioblastoma-initiating cells as a mechanism for radiation-induced resistance, and test new therapeutics to block such glioma stem cell conversion. In order to achieve these translational research goals of our program, we propose three main projects involving: 1) targeting immunotherapy-induced resistance with DC vaccination and PD-1/CSF-1R inhibition; 2) overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma; and 3) strategies against radiation-induced cellular plasticity in glioblastoma. These translational research projects will be supported by four shared resource cores in administration, biospecimen/pathology, neuroimaging, and biostatistics/bioinformatics. Our program has also been successful in actively incorporating researchers in our Developmental Research and Career Enhancement Programs in order to foster new approaches for assessing and treating brain cancer. Our diverse array of novel SPORE projects and state-of-the-art cores has already made a significant impact on brain cancer research during the last funding cycle, and we hope to continue to make impactful contributions to the field well into the future. Each project has been developed jointly by teams of basic and clinical researchers, with the thoughtful advisement of our internal advisory board (IAB) and external advisory board (EAB), working together in a trans-disciplinary manner to address the most vexing problem in brain cancer – the development of treatment resistance. All three proposed projects are highly translational and will reach new human endpoints within the context of our next SPORE grant period.


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	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	000	8	2/19/2025	NON-COMPETING CONTINUATION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	002	8	6/16/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	001	8	5/23/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $2,198,594 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	002	8	8/28/2024	SUPPLEMENT FOR EXPANSION	$86,121
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	003	8	9/9/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	001	8	8/8/2024	NON-COMPETING CONTINUATION	$2,112,473
2024	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	000	7	4/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,198,594

Issue Date FY: 2023 ( Subtotal = $2,282,036 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	003	7	8/14/2023	NON-COMPETING CONTINUATION	$2,046,404
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	004	7	8/15/2023	SUPPLEMENT FOR EXPANSION	$235,632
2023	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	002	6	3/14/2023	COMPETING CONTINUATION	$56
2023	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	001	5	3/14/2023	SUPPLEMENT FOR EXPANSION	-$5
2023	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	000	5	3/14/2023	NON-COMPETING CONTINUATION	-$51
														Subtotal = $2,282,036

Issue Date FY: 2022 ( Subtotal = $2,046,459 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	003	6	9/21/2022	COMPETING CONTINUATION	$44,008
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	002	6	8/4/2022	COMPETING CONTINUATION	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	001	6	7/29/2022	COMPETING CONTINUATION	$2,002,451
2022	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	000	5	2/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,046,459

Issue Date FY: 2021 ( Subtotal = $2,353,029 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	002	5	9/8/2021	SUPPLEMENT FOR EXPANSION	$214,029
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Centers Support Grants	001	5	7/30/2021	NON-COMPETING CONTINUATION	$2,139,000
2021	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	000	4	4/22/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,353,029

Issue Date FY: 2020 ( Subtotal = $2,185,000 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	000	4	7/29/2020	NON-COMPETING CONTINUATION	$2,185,000
														Subtotal = $2,185,000

Issue Date FY: 2019 ( Subtotal = $2,139,000 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	001	3	7/24/2019	NON-COMPETING CONTINUATION	$2,139,000
2019	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	000	2	4/1/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,139,000

Issue Date FY: 2018 ( Subtotal = $2,300,000 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	000	2	7/30/2018	NON-COMPETING CONTINUATION	$2,300,000
														Subtotal = $2,300,000

Issue Date FY: 2017 ( Subtotal = $2,185,000 )
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Centers Support Grants	000	1	8/11/2017	NEW	$2,185,000
														Subtotal = $2,185,000

Grand Total All Awards = $17,689,118

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Investigating Mechanisms of Adaptive Immune Resistance to Combination Immunotherapy within the Glioblastoma Microenvironment

Award Number: P50CA211015

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/11/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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