Thursday, November 21, 2024 11/21/2024

Consolidated Basic Cancer Research Program

Award Number: P30CA010815
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Immune therapy in cancer has made great strides in the past decade. However, not all tumor types benefit from current therapies. Additionally overcoming resistance to both targeted and immune therapy for second- or third- line therapies remains a critical challenge for all cancers. Developing experimental models to advance new immune therapy strategies has faced impediments, hindering progress. Most studies require clinical trials for even minor advancements in approaches, protocols, timing, dosage, and sequential treatments. Our laboratory has developed a new experimental model of immune cell-tumor interactions that will fill an important gap in immune oncology investigations because it is: i) autologous, as immune and tumor cells are derived from the same patients; and ii) reproducible, as tumor cells and iPS (induced pluripotent stem) cells have unlimited growth capacities. The source of melanoma cells are the patients’ lesions, which are maintained as PDX (patient- derived xenografts), organoids, or cell lines. iPS cells are conveniently derived from peripheral blood mononuclear cells or normal fibroblasts. Three cell types, monocytes, pre-T cells and thymic epithelial cells, are independently developed from the same iPS cultures. The monocytes are loaded with tumor antigens (tumor cells, extracts, proteins, or peptides), acting as antigen presenting cells. When the three cell types are placed together as thymic organoids, the T cells mature and appear stable and can be expanded. The first aim proposes to investigate T cell receptor diversity and achieving tumor specificity. The second aim characterizes tumor cell-T cell interactions and how the system can be used to overcome resistance to both checkpoint inhibitors and targeted therapies. We plan to develop melanoma cell-iPS cell pairs from patients resistant to checkpoint inhibitors including anti-PD1 and/or CTLA4 and those who are resistant to both targeted and immune checkpoint therapies. We will then develop complex organoids with stromal and immune cells to mimic tumor-T cell interactions within an intact microenvironment. Finally, we will transfer the in vitro model to an in vivo setting using our extensive experience in humanizing mice. Furthering our on-going collaboration with NCI’s Patient-Derived Models Repository (PDMR) will enable us to expand the technology and conduct critical research aimed at developing new approaches to overcome therapy resistance. Moreover, this collaboration will allow for sharing our new models with the scientific community and extending this innovative approach from melanoma to other malignancies. 1


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 = $3,583,734 )
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	55	3/11/2024	EXTENSION WITH OR WITHOUT FUNDS	$8,371
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	003	55	5/29/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	005	55	9/23/2024	EXTENSION WITH OR WITHOUT FUNDS	$141,689
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	55	5/9/2024	EXTENSION WITH OR WITHOUT FUNDS	$141,684
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	55	2/29/2024	EXTENSION WITH OR WITHOUT FUNDS	$2,541,991
2024	2024	THE WISTAR INSTITUTE OF ANATOMY AND BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	004	55	8/23/2024	SUPPLEMENT FOR EXPANSION	$749,999
														Subtotal = $3,583,734

Issue Date FY: 2023 ( Subtotal = $2,964,875 )
2023	2023	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	54	3/2/2023	SUPPLEMENT FOR EXPANSION	$249,893
2023	2023	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	54	2/28/2023	NON-COMPETING CONTINUATION	$2,714,982
														Subtotal = $2,964,875

Issue Date FY: 2022 ( Subtotal = $2,839,139 )
2022	2022	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	53	9/21/2022	SUPPLEMENT FOR EXPANSION	-$124,157
2022	2022	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	53	2/11/2022	NON-COMPETING CONTINUATION	$2,714,982
2022	2022	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	53	9/19/2022	SUPPLEMENT FOR EXPANSION	$248,314
														Subtotal = $2,839,139

Issue Date FY: 2021 ( Subtotal = $2,714,982 )
2021	2021	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	52	2/26/2021	NON-COMPETING CONTINUATION	$2,714,982
														Subtotal = $2,714,982

Issue Date FY: 2020 ( Subtotal = $2,924,730 )
2020	2020	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	51	4/15/2020	NON-COMPETING CONTINUATION	$2,719,954
2020	2020	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	51	9/2/2020	SUPPLEMENT FOR EXPANSION	$100,000
2020	2020	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	51	4/16/2020	SUPPLEMENT FOR EXPANSION	$104,776
														Subtotal = $2,924,730

Issue Date FY: 2019 ( Subtotal = $2,842,953 )
2019	2019	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	50	6/26/2019	COMPETING CONTINUATION	$185,267
2019	2019	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	50	5/8/2019	SUPPLEMENT FOR EXPANSION	$93,642
2019	2019	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	50	4/17/2019	COMPETING CONTINUATION	$2,749,311
2019	2018	WISTAR INSTITUTE OF ANATOMY AND BIOLOGY, THE	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	003	49	6/26/2019	SUPPLEMENT FOR EXPANSION	-$185,267
														Subtotal = $2,842,953

Issue Date FY: 2018 ( Subtotal = $2,988,079 )
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	004	49	7/23/2018	SUPPLEMENT FOR EXPANSION	$200,000
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	49	2/27/2018	SUPPLEMENT FOR EXPANSION	$128,248
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	49	2/26/2018	NON-COMPETING CONTINUATION	$2,381,024
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	003	49	5/28/2018	SUPPLEMENT FOR EXPANSION	$14,250
2018	2018	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	49	5/23/2018	NON-COMPETING CONTINUATION	$264,557
														Subtotal = $2,988,079

Issue Date FY: 2017 ( Subtotal = $2,788,079 )
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	003	48	7/7/2017	SUPPLEMENT FOR EXPANSION	$14,250
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	48	6/9/2017	NON-COMPETING CONTINUATION	$264,558
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	48	3/6/2017	SUPPLEMENT FOR EXPANSION	$128,248
2017	2017	WISTAR INSTITUTE OF ANATOMY & BIOLOGY	3601 SPRUCE ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	48	2/21/2017	NON-COMPETING CONTINUATION	$2,381,023
														Subtotal = $2,788,079

Issue Date FY: 2016 ( Subtotal = $2,788,079 )
2016	2016	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	47	3/2/2016	SUPPLEMENT FOR EXPANSION	$142,498
2016	2016	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	47	2/18/2016	NON-COMPETING CONTINUATION	$2,645,581
														Subtotal = $2,788,079

Issue Date FY: 2015 ( Subtotal = $2,717,095 )
2015	2015	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	46	3/26/2015	SUPPLEMENT FOR EXPANSION	$138,748
2015	2015	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	46	3/12/2015	NON-COMPETING CONTINUATION	$2,578,347
														Subtotal = $2,717,095

Issue Date FY: 2014 ( Subtotal = $2,609,010 )
2014	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	001	45	7/1/2014	COMPETING CONTINUATION	$2,495,130
2014	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	45	8/21/2014	SUPPLEMENT FOR EXPANSION	$92,630
2014	2014	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	003	45	9/23/2014	COMPETING CONTINUATION	$21,250
2014	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	44	6/24/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,609,010

Issue Date FY: 2013 ( Subtotal = $2,425,333 ) (Continued on the next page)
2013	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	000	44	2/22/2013	NON-COMPETING CONTINUATION	$1,110,965
2013	2013	WISTAR INSTITUTE	36TH AT SPRUCE	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cancer Centers Support Grants	002	44	6/28/2013	SUPPLEMENT FOR EXPANSION	$60,689
Grand Total All Awards = $71,256,725

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Consolidated Basic Cancer Research Program

Award Number: P30CA010815

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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