Tuesday, July 1, 2025 7/1/2025

Therapeutically harnessing anti-viral resident memory T cells in solid tumors

Award Number: R01CA269455
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Therapeutically harnessing anti-viral resident memory T cells in solid tumors - PROJECT SUMMARY/ABSTRACT Recent studies have revealed an abundance of resident memory T cells (TRM) specific for viral infections in a wide range of tumors, often outnumbering cancer-specific T cells. As these cells lack specificity to tumor antigens, they are spared from the hallmark exhaustion/dysfunction of tumor-specific T cells. To this end, we developed a novel immunotherapy which taps into immunostimulatory virus-specific TRM functions through treatment with viral peptides to break the immunosuppressive tumor environment. Reactivating virus-specific TRM with peptide was sufficient to restrict tumor growth in mice and when combined with checkpoint blockade, promoted durable tumor clearance. Mice that cleared tumors were protected from tumor re-challenge, suggesting anti-tumor immunity was established. Virus-specific TRM represent a major part of the tumor immune environment and can be leveraged therapeutically, yet there is a clinically significant gap in knowledge regarding the mechanisms of tumor clearance and how to optimally harness these cells. The objectives in this proposal are to determine (i) mechanism of tumor cell killing and durable tumor immunity, (ii) the impact of viral specificity on TRM function and therapeutic efficacy, and iii) define the optimal modality to reactivate virus-specific TRM. Using both mouse and human systems, this study addresses an innovative perspective connecting antiviral memory cells to tumor immunotherapy using cutting edge methods. We will complement mouse studies with combinatorial tetramer staining to enable simultaneous profiling of T cells specific for an expanded panel of viruses and vaccines in patient tumors. Completion of these aims will advance our understanding of tumor immunosurveillance and TRM function in mice and humans, and identify new target T cell populations for tumor immunotherapy. This contribution is expected to be significant because it will provide a strong scientific framework to expand the efficacy and utility of virus-specific TRM therapy, and enable the development of novel strategies leveraging these potent immune activating cells.


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 = $525,763 )
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	001	3	12/23/2024	SUPPLEMENT FOR EXPANSION	$30,886
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	000	3	12/20/2024	NON-COMPETING CONTINUATION	$445,390
2025	2025	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	002	3	6/25/2025	NON-COMPETING CONTINUATION	$49,487
														Subtotal = $525,763

Issue Date FY: 2024 ( Subtotal = $543,893 )
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	003	2	4/16/2024	NON-COMPETING CONTINUATION	$24,951
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	004	2	4/16/2024	SUPPLEMENT FOR EXPANSION	$3,674
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	002	2	1/5/2024	SUPPLEMENT FOR EXPANSION	$66,097
2024	2024	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	001	2	12/22/2023	NON-COMPETING CONTINUATION	$449,171
2024	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	000	1	11/3/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $543,893

Issue Date FY: 2023 ( Subtotal = $545,793 )
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	000	1	12/19/2022	NEW	$506,676
2023	2023	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Cancer Treatment Research	001	1	9/20/2023	SUPPLEMENT FOR EXPANSION	$39,117
														Subtotal = $545,793

Grand Total All Awards = $1,615,449

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Therapeutically harnessing anti-viral resident memory T cells in solid tumors

Award Number: R01CA269455

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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