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Immunotherapeutic targeting of gangliosides in Ewing Sarcoma

Award Number: U01CA281840
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/19/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Immunotherapeutic targeting of gangliosides in Ewing Sarcoma - Project Summary Ewing sarcoma (EWS) is the second most common tumor involving bone in children and young adults and is fatal in most patients with metastatic or relapsed disease. Patients who survive are left with a lifetime of late effects from the toxic therapy they receive. There have been no new, successful targeted drugs developed to treat EWS for nearly forty years, and we have reached the limit on how much we can intensify chemotherapy treatments. New therapeutic approaches are necessary to prevent relapse and cure more patients. Immunotherapy has altered the treatment landscape for many adult solid tumors but has not yet mediated substantial benefit for children with EWS. Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of children with relapsed leukemia and lymphoma. Recently, we found that CAR T cells targeting GD2, a sugar expressed on the surface of many pediatric cancers, are active in children with incurable brain tumors. This proposal focuses on applying GD2 CAR T cells to EWS. Because GD2 is heterogeneously expressed on EWS, we will explore multiple mechanisms to effectively apply CAR T cells in this disease: 1) targeting a closely related ganglioside that is highly expressed when GD2 is low and 2) utilizing epigenetic inhibitors to significantly increase GD2, making CAR T cells better able to recognize tumor cells. In Aim 1, we will define the expression of gangliosides and their related synthase enzymes on patient tissues and test CARs against an alternative ganglioside. In Aim 2, we will utilize epigenetic inhibitors to increase GD2 on EWS tumors in vitro and in vivo. In Aim 3, we will test combinatorial approaches of CAR T cells and epigenetic inhibitors. Successful completion of these studies will result in new therapeutic options for children with Ewing sarcoma.


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 = $767,167 )
2025	2025	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	3	9/4/2025	NON-COMPETING CONTINUATION	$767,167
														Subtotal = $767,167

Issue Date FY: 2024 ( Subtotal = $755,393 )
2024	2024	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	8/14/2024	NON-COMPETING CONTINUATION	$755,393
														Subtotal = $755,393

Issue Date FY: 2023 ( Subtotal = $795,150 )
2023	2023	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	9/19/2023	NEW	$795,150
														Subtotal = $795,150

Grand Total All Awards = $2,317,710

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Immunotherapeutic targeting of gangliosides in Ewing Sarcoma

Award Number: U01CA281840

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/19/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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