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CAR T platform to treat solid tumors

Award Number: R43CA271880
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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CAR T platform to treat solid tumors - SUMMARY Cancer is one of the leading causes of death worldwide. Over the years, several treatment approaches have been developed. However, their effectiveness is severely limited by the heterogeneity of cancer cells. Thus, there is a constant need for development of therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient's immune system. Of note, renal cell carcinoma and ovarian cancer are considered immunogenic, or “hot” cancers, in that tumors are infiltrated with T cells. This provides optimism that the immune system can be harnessed to be a potent and durable weapon against these cancers. Chimeric antigen receptor (CAR) T cell therapy has shown remarkable efficacy against hematologic tumors. Yet, CAR T cells fail against solid tumors due to key obstacles presented by the tumor microenvironment (TME). We propose in this application to demonstrate proof-of-concept of a novel platform that can overcome the current barrier to CAR T cell therapy in solid tumors. Our strategy combines the specificity of anti-TIM1 CAR with modulation of the TME by a combination of two cytokines, leading to a shift from immunosuppressive to a cytotoxic environment. Our approach capitalizes on the recruitment and activation of a broad repertoire of endogenous innate and adaptive immune cells, including tumor-specific T cells. Super2 and IL-33 CAR T cells promote antitumor immunity in multiple murine solid tumor models and is impervious to antigen loss, highlighting its potential as a universal CAR T cell platform for treatment of solid tumors. Aims will include the following: Aim 1. Design and evaluate human constructs expressing anti-TIM1 CAR, Super2 and IL-33 in vitro. Aim 2. Demonstrate proof of concept (POC) of efficacy of a dual cytokine delivery by anti-TIM1 CAR T cells in a humanized model of Renal cell carcinoma (RCC).


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 = $0 )
2024	2022	CELDARA MEDICAL, LLC	16 CAVENDISH CT STE 240	LEBANON	NH	03766	GRAFTON	USA	Cancer Treatment Research	000	1	4/26/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $368,052 )
2022	2022	CELDARA MEDICAL, LLC	16 CAVENDISH CT	LEBANON	NH	03766	GRAFTON	USA	Cancer Treatment Research	000	1	7/25/2022	NEW	$368,052
														Subtotal = $368,052

Grand Total All Awards = $368,052

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CAR T platform to treat solid tumors

Award Number: R43CA271880

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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