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Delineating Functional Immunity via Image-Guided PET

Award Number: R37CA220482
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Delineating Functional Immunity via Image-Guided PET - Abstract Immunotherapy has made an enormous impact in the treatment of multiple types of cancer, however most patients fail to benefit and methods to monitor response are lacking. To bridge this gap, we have developed non-invasive positron emission tomography (PET) tracers to interrogate immune activity in the tumor microenvironment. Immune cell release of interferon-γ (IFN-γ) is a hallmark of CD8+ cytotoxic T cell (CTL) and Th1-mediated immune activity, both of which contribute to anti-tumor immunity. Our results thus far show that antibody-based immunoPET tracers targeting IFN-γ can detect anti-tumor immunity after administration of immunotherapy, which correlates to treatment outcomes in preclinical tumor models. The current proposal will advance these studies by examining the potential of IFN-γ PET as a pre-treatment predictor of immunotherapy response. We will utilize novel Collaborative Cross recombinant inbred mouse models developed during the course of this project, which exhibit a wide range of response rates to immune checkpoint inhibitors (ICI) due to select variants in their genetic background. These models mimic the diversity of the human population, yet limit tumor heterogeneity as a variable by utilizing genetically identical tumor lines, allowing us to focus on the role of host immunity. We find pre-existing intratumoral IFN-γ expression correlates to ICI outcomes in these models, and we will now test whether IFN-γ PET imaging prior to therapy is predictive of ICI response. Positive results will support the use of IFN-γ PET as part of the formulation of patient treatment strategy. In a necessary step for clinical translation, we will also prepare to submit an investigational new drug (IND) application. Dosimetry, stability studies, and toxicology will be performed. Collectively, the proposed studies will support the clinical use of IFN-γ PET to address critical unmet needs, including predictive biomarker discovery and treatment monitoring technology for cancer immunotherapy. While this proposal focuses on oncology, immune monitoring technologies may also have additional application in multiple inflammatory and autoimmune conditions.


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: 2026 ( Subtotal = $0 )
2026	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	7	11/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	5	2/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $553,790 )
2024	2024	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	7	7/12/2024	NON-COMPETING CONTINUATION	$553,790
														Subtotal = $553,790

Issue Date FY: 2023 ( Subtotal = $578,749 )
2023	2023	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	6	8/16/2023	EXTENSION WITH OR WITHOUT FUNDS	$578,749
														Subtotal = $578,749

Issue Date FY: 2022 ( Subtotal = $536,875 )
2022	2022	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	5	8/14/2022	NON-COMPETING CONTINUATION	$536,875
														Subtotal = $536,875

Issue Date FY: 2021 ( Subtotal = $539,930 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	4	7/21/2021	NON-COMPETING CONTINUATION	$539,930
														Subtotal = $539,930

Issue Date FY: 2020 ( Subtotal = $556,992 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	3	7/27/2020	NON-COMPETING CONTINUATION	$556,992
														Subtotal = $556,992

Issue Date FY: 2019 ( Subtotal = $549,663 )
2019	2019	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	2	6/25/2019	NON-COMPETING CONTINUATION	$549,663
														Subtotal = $549,663

Issue Date FY: 2018 ( Subtotal = $566,226 )
2018	2018	WAYNE STATE UNIVERSITY	5057 WOODWARD 13 FLOOR	DETROIT	MI	48202	WAYNE	USA	Cancer Detection and Diagnosis Research	000	1	7/26/2018	NEW	$566,226
														Subtotal = $566,226

Grand Total All Awards = $3,882,225

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Delineating Functional Immunity via Image-Guided PET

Award Number: R37CA220482

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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