Friday, April 26, 2024 4/26/2024

Admin. Suppl. for NCI CCSG/Moonshot Grant to Develop Immune Radiation Response Index (iRRI) for Immune Cells from Normal and Tumor Microenvironments

Award Number: P30CA016058
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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SUMMARY This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 21-083. The interplay between radiation therapy (RT) in cancer treatment and the host immune system is complex. RT can have local therapeutic effects through direct damage to cancer cells, or can stimulate a systemic anti-tumor immune response. The benefits of combining RT and immunotherapy have been reported in several pre-clinical models and case reports. However, despite the sustained and deep responses observed in some patients, many cancer patients do not respond to these agents emphasizing the need for further improvements in treatment strategies. Interestingly, the effects of radiation on the TME vary with dose and fractionation schedules. In addition to its role in immune activation, RT can also cause chronic inflammation, release of cytokines, and increased infiltration of immunosuppressive cells in the TME potentially rendering decreased tumor responses in a paradoxical manner. However, knowledge is lacking on the immunologic impact of different RT regimens, especially in comparison with changes to RT in human tumor tissues. This proposal aims to investigate the effects of different doses and fractionation of RT on innate and adaptive immune cells using both pre-clinical syngeneic murine melanoma and non-small cell lung cancer (NSCLC) flank models. We will correlate and compare these changes to those within formalin-fixed paraffin-embedded (FFPE) tissue surgical samples from human patients with brain metastases from melanoma and NSCLC recently treated with RT or non-irradiated patient samples. Comparing with non-irradiated control samples, we will determine the effects of RT on tumor immunogenicity (PD-L1, MHC Class I levels) and on immune cell absolute numbers in the tumor microenvironment (TME). Using a multispectral imaging technique, we will measure RT induced CD4+ T cell, CD8+ effector T cells, regulatory T cells, myeloid derived suppressor cells (MDSCs), tumor associated macrophages (TAMs), and dendritic cell influx into the TME and secondary lymphoid tissues in animal models. Serum cytokine levels following RT will also be measured using cytokine array multiplex panels. Similarly, a multispectral imaging technique will measure RT induced changes to immune cell populations in human tumor surgical specimens. Since RT can induce changes in the gene and protein expression profiles of both tumor and immune cells, and transcriptomic landscapes can be associated therapeutic outcomes, the cell-type specific transcriptional profile in the TME of FFPE human tumor samples will be determined using single cell transcriptomic assays. Our multi-disciplinary team plans to systematically categorize the effects of different RT regimens on immune cells and define a radiation response index (i-RRI) on a dose scale (in Gy). We aim to define immune cells as being either “radiation sensitive” or “radiation resistant” at particular doses and fractionation schedules of RT, compared to non-irradiated controls, based on their contribution to eliciting a potential anti-tumor immune response within the TME.


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 = $5,154,649 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	48	12/12/2023	NON-COMPETING CONTINUATION	$5,154,649
														Subtotal = $5,154,649

Issue Date FY: 2023 ( Subtotal = $5,861,638 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	47	1/26/2023	NON-COMPETING CONTINUATION	$5,727,388
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	47	9/18/2023	SUPPLEMENT FOR EXPANSION	$134,250
2023	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	46	6/7/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $5,861,638

Issue Date FY: 2022 ( Subtotal = $6,106,613 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	008	46	2/4/2022	SUPPLEMENT FOR EXPANSION	$107,503
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	007	46	1/20/2022	NON-COMPETING CONTINUATION	$5,731,766
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	010	46	8/25/2022	SUPPLEMENT FOR EXPANSION	$100,000
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	011	46	9/26/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	009	46	2/11/2022	SUPPLEMENT FOR EXPANSION	$167,344
2022	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	006	45	10/12/2021	COMPETING CONTINUATION	$1,062,405
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	005	44	10/12/2021	SUPPLEMENT FOR EXPANSION	-$150,000
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	003	44	10/12/2021	SUPPLEMENT FOR EXPANSION	-$276,109
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	44	10/12/2021	SUPPLEMENT FOR EXPANSION	-$115,001
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	004	44	10/12/2021	SUPPLEMENT FOR EXPANSION	-$299,186
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	44	10/12/2021	SUPPLEMENT FOR EXPANSION	-$156,000
2022	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	44	10/12/2021	NON-COMPETING CONTINUATION	-$66,109
														Subtotal = $6,106,613

Issue Date FY: 2021 ( Subtotal = $6,037,919 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	45	1/25/2021	COMPETING CONTINUATION	$5,751,010
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	45	9/10/2021	SUPPLEMENT FOR EXPANSION	$10,800
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	45	9/13/2021	SUPPLEMENT FOR EXPANSION	$276,109
														Subtotal = $6,037,919

Issue Date FY: 2020 ( Subtotal = $6,037,112 )
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	44	12/18/2019	SUPPLEMENT FOR EXPANSION	$0
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	006	44	9/10/2020	SUPPLEMENT FOR EXPANSION	$150,000
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	005	44	9/9/2020	SUPPLEMENT FOR EXPANSION	$276,109
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	44	12/6/2019	SUPPLEMENT FOR EXPANSION	$115,001
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Treatment Research	004	44	9/3/2020	SUPPLEMENT FOR EXPANSION	$299,186
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	003	44	6/3/2020	SUPPLEMENT FOR EXPANSION	$156,000
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	44	11/26/2019	NON-COMPETING CONTINUATION	$5,040,816
														Subtotal = $6,037,112

Issue Date FY: 2019 ( Subtotal = $5,448,579 )
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	004	43	9/13/2019	SUPPLEMENT FOR EXPANSION	$12,876
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	43	9/3/2019	SUPPLEMENT FOR EXPANSION	$59,999
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	003	43	9/4/2019	SUPPLEMENT FOR EXPANSION	$85,232
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	43	8/30/2019	SUPPLEMENT FOR EXPANSION	$51,088
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	005	43	9/16/2019	SUPPLEMENT FOR EXPANSION	$198,568
2019	2019	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	43	12/31/2018	NON-COMPETING CONTINUATION	$5,040,816
														Subtotal = $5,448,579

Issue Date FY: 2018 ( Subtotal = $5,083,268 )
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	000	42	1/25/2018	NON-COMPETING CONTINUATION	$4,294,526
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	005	42	9/7/2018	SUPPLEMENT FOR EXPANSION	$114,309
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	004	42	9/6/2018	SUPPLEMENT FOR EXPANSION	$50,569
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	001	42	3/29/2018	SUPPLEMENT FOR EXPANSION	$59,783
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	003	42	6/21/2018	SUPPLEMENT FOR EXPANSION	$59,999
2018	2018	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	002	42	5/23/2018	NON-COMPETING CONTINUATION	$504,082
														Subtotal = $5,083,268

Issue Date FY: 2017 ( Subtotal = $5,505,690 ) (Continued on the next page)
2017	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	005	41	6/28/2017	SUPPLEMENT FOR EXPANSION	$10,554
2017	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	004	41	6/7/2017	NON-COMPETING CONTINUATION	$504,082
2017	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	007	41	6/28/2017	SUPPLEMENT FOR EXPANSION	$20,000
2017	2017	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Cancer Centers Support Grants	006	41	6/28/2017	SUPPLEMENT FOR EXPANSION	$12,498
Grand Total All Awards = $117,469,096

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Admin. Suppl. for NCI CCSG/Moonshot Grant to Develop Immune Radiation Response Index (iRRI) for Immune Cells from Normal and Tumor Microenvironments

Award Number: P30CA016058

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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