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Allogeneic BAFF Ligand Based CAR T Cells as a Novel Therapy for B Cell Malignancies

Award Number: R44CA278021
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Allogeneic BAFF Ligand Based CAR T Cells as a Novel Therapy for B Cell Malignancies - ABSTRACT Since the first FDA approval of chimeric antigen receptor (CAR) T cell therapy in 2017, the use of engineered T cells expressing specific CARs to treat cancer has generated durable cures for many patients. Nevertheless, a significant subset of patients with B cell malignancies relapse following treatment due to lack of CAR T cell persistence and the ability of cancer cells to change with time and evade therapeutic interventions. Autologous T cell therapies also carry significant timeline and cost burdens, making widespread adoption difficult. In this application, we propose a novel allogeneic CAR T cell therapy aimed at improving outcomes for patients with mantle cell lymphoma (MCL) by overcoming deficiencies present in current generation CD19 targeted therapeutics. B cell activating factor (BAFF) provides critical survival signals to both normal and neoplastic B cells through a family of receptors (BAFF receptor, TACI, and BCMA) thus mitigating potential for antigen escape. BAFF and its receptors have remained underexplored in the context of B cell malignancies where strategies have relied overwhelmingly on pan B cell antigens such as CD19 and CD20. Since BAFF binds its receptors with moderate affinity, we believe this will increase the ability of these cells to form memory populations and engage in serial killing. We will leverage this ligand-based CAR design in an allogeneic gamma delta (γδ) T cell platform, as γδ T cells have been shown to have high replicative properties in vitro and do not mediate graft versus host disease in new hosts. We have produced preliminary data that confirms our ability to use the non- viral TcBuster DNA transposon system to generate T cells with BAFF-CAR expression. The overall objective of this proposal is to further develop and evaluate our γδ BAFF-CAR T cell therapy for the treatment of MCL in IND enabling studies. In doing so, our allogeneic BAFF-CAR T cell therapy supports an urgently needed shift in therapeutic development toward new tumor antigens that protect against antigen escape while reducing the manufacturing burden associated with cellular therapies through use of a readily available cell source.


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 = $1,463,315 )
2025	2025	LUMINARY THERAPEUTICS, INC.	1200 WASHINGTON AVE S STE 260	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Cancer Treatment Research	000	2	9/23/2025	EXTENSION WITH OR WITHOUT FUNDS	$1,463,315
														Subtotal = $1,463,315

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	LUMINARY THERAPEUTICS, INC.	1200 WASHINGTON AVE S STE 260	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Cancer Treatment Research	000	1	1/29/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $397,934 )
2023	2023	LUMINARY THERAPEUTICS, INC.	1200 WASHINGTON AVE S STE 260	MINNEAPOLIS	MN	55415	HENNEPIN	USA	Cancer Treatment Research	000	1	6/30/2023	NEW	$397,934
														Subtotal = $397,934

Grand Total All Awards = $1,861,249

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Allogeneic BAFF Ligand Based CAR T Cells as a Novel Therapy for B Cell Malignancies

Award Number: R44CA278021

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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