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Photodynamic Priming of Cancer and Image-guidance for Optimal Immune Response

Award Number: P01CA084203
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/1999
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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Photodynamic Priming of Cancer and Image-guidance for Optimal Immune Response - OVERALL PROGRAM SUMMARY For optimal cancer therapy, combination approaches that are mechanistically complementary and directed at non-overlapping molecular targets are needed. Strategically, combinations should be selected such that the first treatment primes the tumor for the second treatment. Building upon our own findings and work on photodynamic therapy (PDT) in pancreatic adenocarcinoma (PDAC) and nonmelanoma skin cancer (NMSC), along with recent advances in immunotherapy, we hypothesize that the damage-related processes triggered by PDT can form the basis for Photodynamic Priming (PDP) to promote an immune-based combination therapy. PDP induces immunogenic cell death, enhances influx of tumor infiltrating lymphocytes (TILs), and sensitizes the tumor microenvironment to immune checkpoint inhibition (ICI). We will capture the PDP effect to design a non-empiric approach for PDT-ICI combination therapy. We will be helped in this effort by our recent innovation of hyperspectral confocal imaging that can monitor 6 biomarkers simultaneously in live tumor bearing animals, and allow quantification of TIL subsets along with PD1/PD-L1 expression changes. We posit that ICI will be most beneficial when immunologically “cold” tumors can first be converted to “hot” tumors via PDP treatment, thereby minimizing the ICI dose required and reducing toxicity. Our Program has 3 Research Projects and 2 scientific Cores, plus an Administrative Core. Projects 1 and 2 are largely clinical while Project 3 is exclusively pre-clinical, driving fundamental findings that form the basis of the hypothesis. Project 1 introduces a double-priming strategy for the treatment of NMSC; the tumor is first treated pharmaco- logically with 5-fluorouracil or Vitamin D to enhance PDT priming, which in turn increases the efficacy of ICI. Project 2 focuses on PDP in pancreatic cancer patients who are unresponsive to chemotherapy. PDT is delivered under endoscopic ultrasound (EUS) guidance, and timing of ICI delivery is informed by findings from Project 3 and by examining subpopulations of TILs in metastatic lymph nodes in some patients. Project 3 looks in-depth at PDP induction of TILs in a PDAC murine model, and in patient-derived immune organoids (PDIO’s). Cores are critical. Core B will assist Projects 1 and 3 with high resolution imaging in preclinical models and PDIOs, and Core C will support all projects with dosimetry techniques to monitor tumor treatment response, including radiomics to garner new information from CT scans in PDAC patients. We propose t h a t new combinations o f PDT with immune checkpoint inhibition (ICI), if done in a rational way that is informed by optical imaging to monitor molecular responses at the cellular level and in real time, will reduce a major barrier to ICI therapy (the lack of effective immune cell infiltration into the tumor). Impact and Relevance: This program positively impacts the treatment of two cancers, PDAC and NMSC, at opposite ends of the spectrum of high mortality/morbidity and high incidence. Both cancers inflict a heavy societal burden of cost and suffering. Findings from this work could also be translatable to other types of cancer.


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 = $1,206,614 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	20	3/6/2026	NON-COMPETING CONTINUATION	$1,206,614
														Subtotal = $1,206,614

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	19	9/12/2025	NON-COMPETING CONTINUATION	$0
2025	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	19	3/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,002,287 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	19	9/19/2024	NON-COMPETING CONTINUATION	$1,002,287
														Subtotal = $1,002,287

Issue Date FY: 2023 ( Subtotal = $1,202,445 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	18	9/21/2023	NON-COMPETING CONTINUATION	$24,048
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	18	9/13/2023	NON-COMPETING CONTINUATION	$1,178,397
														Subtotal = $1,202,445

Issue Date FY: 2022 ( Subtotal = $1,274,917 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	17	9/15/2022	COMPETING CONTINUATION	$1,274,917
														Subtotal = $1,274,917

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	16	9/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,035,201 )
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	16	1/14/2020	NON-COMPETING CONTINUATION	$103,521
2020	2020	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	16	12/31/2019	NON-COMPETING CONTINUATION	$931,680
														Subtotal = $1,035,201

Issue Date FY: 2019 ( Subtotal = $366,904 )
2019	2019	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	15	6/28/2019	NON-COMPETING CONTINUATION	$366,904
														Subtotal = $366,904

Issue Date FY: 2018 ( Subtotal = $1,458,454 )
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	14	3/21/2018	NON-COMPETING CONTINUATION	$1,312,608
2018	2018	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	14	5/23/2018	NON-COMPETING CONTINUATION	$145,846
														Subtotal = $1,458,454

Issue Date FY: 2017 ( Subtotal = $1,421,276 )
2017	2017	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	13	12/30/2016	NON-COMPETING CONTINUATION	$1,279,148
2017	2017	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	13	6/7/2017	NON-COMPETING CONTINUATION	$142,128
														Subtotal = $1,421,276

Issue Date FY: 2016 ( Subtotal = $1,419,849 )
2016	2016	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	12	2/2/2016	NON-COMPETING CONTINUATION	$1,419,849
														Subtotal = $1,419,849

Issue Date FY: 2015 ( Subtotal = $1,477,552 )
2015	2015	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	11	4/3/2015	COMPETING CONTINUATION	$0
2015	2015	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	11	3/11/2015	COMPETING CONTINUATION	$1,477,552
														Subtotal = $1,477,552

Issue Date FY: 2013 ( Subtotal = $1,334,595 )
2013	2013	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	10	7/5/2013	NON-COMPETING CONTINUATION	$624,702
2013	2013	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	10	12/19/2012	NON-COMPETING CONTINUATION	$709,893
														Subtotal = $1,334,595

Issue Date FY: 2012 ( Subtotal = $1,418,960 )
2012	2012	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	9	4/30/2012	NON-COMPETING CONTINUATION	$136,886
2012	2012	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	9	12/30/2011	NON-COMPETING CONTINUATION	$1,282,074
														Subtotal = $1,418,960

Issue Date FY: 2011 ( Subtotal = $1,334,228 )
2011	2011	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	8	12/30/2010	NON-COMPETING CONTINUATION	$1,334,228
														Subtotal = $1,334,228

Issue Date FY: 2010 ( Subtotal = $1,440,392 )
2010	2010	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	7	6/28/2010	NON-COMPETING CONTINUATION	$1,440,392
														Subtotal = $1,440,392

Issue Date FY: 2009 ( Subtotal = $1,452,483 )
2009	2009	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	001	6	2/19/2009	COMPETING CONTINUATION	$1,426,251
2009	2009	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	002	6	7/27/2009	COMPETING CONTINUATION	$26,232
2009	2005	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	5	11/21/2008	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,452,483

Issue Date FY: 2005 ( Subtotal = $1,584,723 )
2005	2005	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	5	9/2/2005	NON-COMPETING CONTINUATION	$1,584,723
														Subtotal = $1,584,723

Issue Date FY: 2004 ( Subtotal = $1,545,620 )
2004	2004	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	4	7/30/2004	NON-COMPETING CONTINUATION	$1,545,620
														Subtotal = $1,545,620

Issue Date FY: 2003 ( Subtotal = $1,497,936 )
2003	2003	MASSACHUSETTS GENERAL HOSPITAL	32 FRUIT STREET	BOSTON	MA	02114	SUFFOLK	USA	Cancer Treatment Research	000	3	7/28/2003	NON-COMPETING CONTINUATION	$1,497,936
														Subtotal = $1,497,936

Grand Total All Awards = $26,653,799

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Photodynamic Priming of Cancer and Image-guidance for Optimal Immune Response

Award Number: P01CA084203

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/1999

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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