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Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy

Award Number: R01CA248111
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy - Project Summary Recently, we discovered that adoptive transfer of CD39KO tumor-specific (mixed CD4+ and CD8+) T cells, resulted in long-term survival of mice bearing large established tumors. Unexpectedly, we found that these T cells promoted killing of antigen-loss-variants (ALVs) in vivo and prevented tumor recurrence. Moreover, transfer of CD39KO, but not control KO, tumor-specific T cells eradicated large chimeric tumors that contained 10% of ALVs and resulted in long-term tumor-free survival and protection against rechallenge with ALV tumor cells. Based on these novel findings, we hypothesize that transfer of tumor-specific CD39KO T cells will eradicate large established tumors and prevent recurrence of ALV tumors, due to their ability to directly kill the tumor cells and induce anti-ALV responses. Aim 1 will determine the contribution of type I IFN production at the tumor site in preventing recurrence of ALV tumors. Aim 2 will determine the role of CD39KO T cells in the recruitment of inflammatory myeloid cells and the induction of type I IFN production for tumor clearance. Aim 3 will determine whether human tumor-specific CD39KO T cells are also endowed with these abilities to effectively eradicate human tumors in humanized mice. These innovative and mechanistic studies will shed light on the mechanisms underlying CD39KO T cell-mediated antitumor immunity and will thus establish a foundation for translating this discovery into more effective immunotherapies using tumor-specific T-cell subsets in human cancers.


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 = $388,825 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	6	8/1/2025	NON-COMPETING CONTINUATION	$388,825
														Subtotal = $388,825

Issue Date FY: 2024 ( Subtotal = $369,383 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	5	7/31/2024	NON-COMPETING CONTINUATION	$369,383
														Subtotal = $369,383

Issue Date FY: 2023 ( Subtotal = $381,049 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	002	4	8/25/2023	NON-COMPETING CONTINUATION	$381,049
2023	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	3	5/18/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$58,321
2023	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	1	5/18/2023	NEW	-$58,321
														Subtotal = $381,049

Issue Date FY: 2022 ( Subtotal = $393,863 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	001	2	9/15/2022	NON-COMPETING CONTINUATION	-$336,255
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	2	12/15/2021	NON-COMPETING CONTINUATION	$336,255
2022	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	002	3	9/15/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$393,863
														Subtotal = $393,863

Issue Date FY: 2021 ( Subtotal = $373,617 )
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	1	12/21/2020	NEW	$373,617
														Subtotal = $373,617

Grand Total All Awards = $1,906,737

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Eradication of Escaped Variant Tumor Cells for Cancer Immunotherapy

Award Number: R01CA248111

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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