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Lymphoid Experimental Therapeutics Platform to Study Cooperative Signaling inHuman Lymphomas

Award Number: R01CA238745
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Lymphoid Experimental Therapeutics Platform to Study Cooperative Signaling inHuman Lymphomas - Approximately 40% of patients with activated B cell (ABC) subtype of diffuse large B cell lymphoma DLBCL relapse or are not curable with current therapies. The mechanism through which ABC-DLBCLs are resistant to current therapies are unknown but may be linked to the particular spectrum of somatic mutations in these tumors, which are in concert with complex growth signals provided by the lymphoid tumor microenvironment (Ly-TME). Many of the hallmark ABC-DLBCL mutations result in constitutive activation of B cell receptor (BCR) and Toll like receptor (TLR) pathways in these malignant immune cells. Hence these pathways are emerging as a source of therapeutic targets for the treatment of ABC-DLBCLs. However, to date, existing BCR pathway inhibitors such as those targeting Bruton’s tyrosine kinase (BTK) are active in a limited subset of patients and only for a short duration (few months), causes of which are unknown. The substantial differences in response rates and response duration between ABC-DLBCL patients reflect the variable dependencies on BCR and TLR signaling and/or differential regulation by the Ly-TME. Therefore, Ly-TME seems essential for ABC-DLBCLs in spite of constitutive action of signaling pathways. ABC-DLBCLs have multiple cooperative and feed-back, and bypass signaling pathways that promote tumor survival and personalized therapy will require combination therapeutics to adequately suppress these networks. Unfortunately, the impact of Ly-TME on these signaling pathways in ABC-DLBCLs and, consequently, on the efficacy of targeted therapeutics are poorly understood. Therefore, the objective of this R01 is to develop an experimental therapeutics technology with Ly-TME and determine the role of Ly-TME on ABC-DLBCL survival, signaling, and response to pathway inhibitors of the Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) paracaspase. By integrating the results of R01, the team will determine the role of Ly-TME in BCR-MALT1 and TLR signaling in ABC- DLBCL and determine a more refined dosing scheme. Mechanisms from this R01 will increase “predictive power” of MALT1 inhibitors, and provide mechanistic clues towards resistance to MALT1 inhibitors, and discover combinatorial therapy to overcome resistance.


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: 2024 ( Subtotal = $405,651 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cancer Treatment Research	000	5	7/1/2024	NON-COMPETING CONTINUATION	$405,651
														Subtotal = $405,651

Issue Date FY: 2023 ( Subtotal = $421,685 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Treatment Research	000	4	6/20/2023	NON-COMPETING CONTINUATION	$421,685
														Subtotal = $421,685

Issue Date FY: 2022 ( Subtotal = $451,764 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Treatment Research	000	3	6/30/2022	NON-COMPETING CONTINUATION	$451,764
														Subtotal = $451,764

Issue Date FY: 2021 ( Subtotal = $473,623 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Treatment Research	000	2	6/11/2021	NON-COMPETING CONTINUATION	$473,623
														Subtotal = $473,623

Issue Date FY: 2020 ( Subtotal = $489,269 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cancer Treatment Research	000	1	6/30/2020	NEW	$489,269
														Subtotal = $489,269

Grand Total All Awards = $2,241,992

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Lymphoid Experimental Therapeutics Platform to Study Cooperative Signaling inHuman Lymphomas

Award Number: R01CA238745

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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