Tuesday, July 1, 2025 7/1/2025

Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancer

Award Number: P50CA136393
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2009
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancer - ABSTRACT With an estimated 20,000 new cases and 13,000 deaths in 2024, ovarian cancers (OCs) remain the deadliest gynecological malignancy. Despite the heterogeneity of this group of cancers in terms of histology, possible cell of origin, and genomic alterations, OCs are almost universally treated with surgery and adjuvant or neoadjuvant chemotherapy that includes the platinum coordination compounds carboplatin or cisplatin. The vast majority of OCs relapse after this treatment and, whether treated with further platinum agents or other therapies, become more resistant with each subsequent therapy. Platinum-resistant ovarian cancer, i.e., ovarian cancer that recurs within 6 months of the most recent platinum-containing therapy, has a median survival of 6-20 months despite the development of newer targeted agents, highlighting the need for improved therapies. In this context, two projects of the Mayo Clinic Ovarian Cancer SPORE (P50 CA136393) are developing and testing two new therapies for platinum-resistant ovarian cancer. Project 2 involves preclinical studies and a phase II clinical trial PLX038, a sustained release formulation of the active TOP1 inhibitor (TOP1i) SN-38. Project 4 involves the development and subsequent phase I clinical testing of natural killer (NK) cells that have been transduced with a chimeric antigen receptor (CAR) targeting mesothelin and modified to sustain their survival and function in vivo. A goal in both projects is identification of OC patients most likely to benefit from these treatments. With previous funding from the NCI Innovative Molecular Analysis Technologies (IMAT) Program, the PIs of this revision project have developed microfluidic devices that permit prolonged survival and proliferation of patient- derived organoids (PDOs) and tumor explants in 3-dimensional culture. A major advantage of these devices is the ability to assess the impact of various treatments, including small molecules and cellular therapies, on both tumor cells and cells in the tumor microenvironment. The revision project will test the hypothesis that responses to therapy in these microfluidic devices correspond to responses of patients treated with the same therapies on the two SPORE-associated clinical trials. In particular, the proposed project will i) compare the TOP1i response of OC patient-derived xenografts (PDXs) treated with PLX038 in vivo with their response, including stabilization of TOP1-DNA covalent complexes and shrinkage, when treated with TOP1i in the microfluidic devices ex vivo (Aim 1); ii) assess the survival, functionality (as measured by cytokine secretion) and killing potency of NK cells expressing CISH miRNA and a MSLN CAR when added to fresh OC explants in the microfluidic devices (Aim 2); and compare the responses of tumor explants cultured with TOP1i or modified MSLN CAR NK cells in microfluidic devices ex vivo with the responses of the source patients to the same treatments in vivo in the course of two SPORE-associated clinical trials (Aim 3). These proposed studies will simultaneously identify whether these devices are able to predict responses to two different types of OC therapy and position the devices as potential companion diagnostics for further development.


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 = $210,627 )
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	14	1/7/2025	SUPPLEMENT FOR EXPANSION	$210,627
2025	2025	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	14	2/12/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	14	12/3/2024	NON-COMPETING CONTINUATION	$0
2025	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	14	1/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $210,627

Issue Date FY: 2024 ( Subtotal = $2,019,803 )
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	004	14	9/5/2024	SUPPLEMENT FOR EXPANSION	$201,750
2024	2024	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	14	8/28/2024	NON-COMPETING CONTINUATION	$1,818,053
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	13	10/11/2023	NON-COMPETING CONTINUATION	$0
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	13	3/1/2024	NON-COMPETING CONTINUATION	$0
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	13	2/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,019,803

Issue Date FY: 2023 ( Subtotal = $1,752,990 )
2023	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	13	9/8/2023	NON-COMPETING CONTINUATION	$1,752,990
2023	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	12	3/21/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	12	4/28/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,752,990

Issue Date FY: 2022 ( Subtotal = $1,749,801 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	003	12	9/22/2022	NON-COMPETING CONTINUATION	$37,721
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	12	9/14/2022	NON-COMPETING CONTINUATION	$1,712,080
2022	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	11	1/31/2022	COMPETING CONTINUATION	$4,187
2022	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	10	1/31/2022	NON-COMPETING CONTINUATION	-$4,187
														Subtotal = $1,749,801

Issue Date FY: 2021 ( Subtotal = $1,762,703 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	11	7/16/2021	COMPETING CONTINUATION	$1,762,703
														Subtotal = $1,762,703

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	10	12/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $2,139,000 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	002	10	9/3/2019	NON-COMPETING CONTINUATION	$2,139,000
2019	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	9	11/5/2018	NON-COMPETING CONTINUATION	$0
2019	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	9	11/7/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,139,000

Issue Date FY: 2018 ( Subtotal = $2,300,000 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	9	8/21/2018	NON-COMPETING CONTINUATION	$2,300,000
														Subtotal = $2,300,000

Issue Date FY: 2017 ( Subtotal = $2,300,000 )
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	8	8/8/2017	NON-COMPETING CONTINUATION	$2,184,999
2017	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	8	9/21/2017	NON-COMPETING CONTINUATION	$115,001
														Subtotal = $2,300,000

Issue Date FY: 2016 ( Subtotal = $2,162,000 )
2016	2016	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	7	8/16/2016	NON-COMPETING CONTINUATION	$2,162,000
														Subtotal = $2,162,000

Issue Date FY: 2015 ( Subtotal = $2,184,999 )
2015	2015	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	6	9/11/2015	COMPETING CONTINUATION	$2,184,999
														Subtotal = $2,184,999

Issue Date FY: 2014 ( Subtotal = $622,294 )
2014	2014	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	5	9/19/2014	SUPPLEMENT FOR EXPANSION	$622,294
														Subtotal = $622,294

Issue Date FY: 2013 ( Subtotal = $2,150,500 )
2013	2013	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	5	8/21/2013	NON-COMPETING CONTINUATION	$2,150,500
														Subtotal = $2,150,500

Issue Date FY: 2012 ( Subtotal = $2,300,000 )
2012	2012	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	4	9/19/2012	NON-COMPETING CONTINUATION	$2,300,000
														Subtotal = $2,300,000

Issue Date FY: 2011 ( Subtotal = $2,185,000 )
2011	2011	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	3	7/21/2011	NON-COMPETING CONTINUATION	$2,185,000
														Subtotal = $2,185,000

Issue Date FY: 2010 ( Subtotal = $2,300,000 )
2010	2010	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	001	2	7/14/2010	NON-COMPETING CONTINUATION	$2,300,000
2010	2009	MAYO CLINIC	200 FIRST STREET	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	1	11/2/2009	NEW	$0
														Subtotal = $2,300,000

Issue Date FY: 2009 ( Subtotal = $2,300,000 )
2009	2009	MAYO CLINIC ROCHESTER	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Cancer Centers Support Grants	000	1	8/18/2009	NEW	$2,300,000
														Subtotal = $2,300,000

Grand Total All Awards = $30,439,717

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Use of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancer

Award Number: P50CA136393

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2009

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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