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Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)

Award Number: U54CA274509
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/22/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics) - Overall Project Summary The proposed U54 program Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor -- Immunotherapy Combinations (ST-Analytics) is designed to develop the recent conceptual advance that targeted inhibitor + cancer immunotherapy (IT) combination treatments may yield significantly greater patient benefit if those treatments are administered in sequence rather than simultaneously. Analysis of retrospective clinical data coupled with in vivo therapeutic modeling using syngeneic models of murine melanoma strongly support this concept. In fact, the picture that has emerged in melanoma is that immune factors can play a strong role in driving resistance to MAPK inhibitor (MAPKi) therapy, and that lead-in immune checkpoint blockade (ICB) can ‘prime’ both the primary tumor and distal metastases (including brain metastases) for eradication when the IT is subsequently combined with MAPKi. This observation opens the doors for immune based strategies, such as ICB or adoptive cell therapy (ACT), as sequential combinatorial agents to prevent MAPKi resistance. However, this concept introduces a number of new variables, including dosing, sequence, and timing. This can make the design and execution of clinical trials that can yield statistically significant outcomes impractical. This is the scientific and translational problem we address in the proposed ST-Analytics U54. The ST-Analytics U54 center is populated by leading scientists at the ISB, the UCLA Geffen School of Medicine, and Yale, and is comprised of two research projects and two research cores, with each project integrating both state-of-the-art experimentation and computational work. This structure is further designed to bring together the scientific, experimental, and computational and administrative resources to develop a data base that captures the kinetics of lead-in monotherapy tumor priming, and apply that data base to the development of predictive in silico models that can inform the design of such targeted inhibitor – immunotherapy sequence combinations for clinical trials. This requires close integration and cycles of iteration between of state-of-the-art experimentation, leading edge computation, and realistic disease models, continuously calibrated through the analysis of highly relevant, biopsied patient tumors. The resulting science also provides exciting opportunities for high impact STEM outreach. We propose to act on those opportunities by leveraging a long-standing systems education outreach program at ISB that already has impacted K-12 STEM education in all 50 states, and places an emphasis on those communities that have been historically under-represented in STEM.


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	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	001	3	5/12/2025	NON-COMPETING CONTINUATION	$0
2025	2024	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	000	3	10/11/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $2,488,322 )
2024	2024	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	003	3	9/12/2024	SUPPLEMENT FOR EXPANSION	$133,520
2024	2024	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	001	2	8/16/2024	SUPPLEMENT FOR EXPANSION	$12,350
2024	2024	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	002	3	9/10/2024	NON-COMPETING CONTINUATION	$2,342,452
2024	2023	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	000	2	6/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,488,322

Issue Date FY: 2023 ( Subtotal = $2,696,226 )
2023	2023	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	001	2	8/30/2023	NON-COMPETING CONTINUATION	$2,548,990
2023	2023	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	002	2	8/31/2023	SUPPLEMENT FOR EXPANSION	$147,236
2023	2022	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	000	1	11/30/2022	NEW	$0
														Subtotal = $2,696,226

Issue Date FY: 2022 ( Subtotal = $2,702,613 )
2022	2022	INSTITUTE FOR SYSTEMS BIOLOGY	401 TERRY AVE N	SEATTLE	WA	98109	KING	USA	Cancer Centers Support Grants	000	1	9/22/2022	NEW	$2,702,613
														Subtotal = $2,702,613

Grand Total All Awards = $7,887,161

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Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)

Award Number: U54CA274509

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/22/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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