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Identification of cancer neoepitope-specific T cells using novel high-throughput hydrogel based platforms

Award Number: R33CA278429
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/08/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Identification of cancer neoepitope-specific T cells using novel high-throughput hydrogel based platforms - Abstract Immunotherapies for cancer, including Adoptive Cell Transfer (ACT), chimeric antigen receptor (CAR) T cell therapy, and Immune Checkpoint Blockade (ICB), have seen great clinical success. However, they are still limited by cost, variable efficacy and resistance, and lack of quality targets. Technologies to track immune responses, and in particular tumor-specific T cell responses, would help researchers and clinicians to better understand variable responses in patients, design better targets for therapies, and track patient health outcomes. In this proposal, we aim to adapt our novel hydrogel-based immune cell expansion system to detect and characterize rare, neo-epitope specific T cells in the peripheral blood. This platform, termed the artificial T cell stimulation matrix (aTM), is a hyaluronic acid hydrogel conjugated with signals 1 (peptide-MHC), 2 (anti-CD28) and 3 (cytokine support). In order to create an aTM-based high- throughput detection system, we will first investigate the effects of physical (i.e. stiffness) and biochemical (i.e. activation molecules and cytokines) cues of the aTM on the expansion of neo- epitope specific anti-tumor T cells in mice. We will test the optimized aTM for batched expansion from bulk murine splenocytes in order to create a high-throughput system. Next, we will develop a process to detect and expand tumor-associated antigen-specific T cells from peripheral blood of healthy donors and compare this to current gold standards of antigen-specific T cell detection. Finally, because disease status may impact our ability to detect rare T cells, we will verify that the system can be used for detection of neoepitope-specific T cells from the peripheral blood of melanoma patients. Access to blood from patients will also allow us to determine how ICB treatment affects the immune response to the tumor by investigation of expanded neo-epitope specific T cell phenotype and function before and after therapy. The development of aTM as a high-throughput detection system for neo-epitope, patient-specific T cell responses will allow pre-clinical and clinical researchers to study immune responses to cancer and to improve cancer immunotherapies by bringing the power of these therapies to more patients.


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: 2026 ( Subtotal = $363,013 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	000	3	2/11/2026	NON-COMPETING CONTINUATION	$363,013
														Subtotal = $363,013

Issue Date FY: 2025 ( Subtotal = $406,871 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	000	2	1/28/2025	NON-COMPETING CONTINUATION	$366,184
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	002	2	8/28/2025	NON-COMPETING CONTINUATION	$0
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	001	2	5/21/2025	NON-COMPETING CONTINUATION	$40,687
														Subtotal = $406,871

Issue Date FY: 2024 ( Subtotal = $428,438 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	1	2/8/2024	NEW	$428,438
														Subtotal = $428,438

Grand Total All Awards = $1,198,322

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Identification of cancer neoepitope-specific T cells using novel high-throughput hydrogel based platforms

Award Number: R33CA278429

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/08/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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