Monday, November 17, 2025 11/17/2025

Investigating immunophenotype and metabolism of TCR KO donor and third-party CD19-targeted chimeric antigen receptor T cells

Award Number: K08HL156082
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/25/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Investigating immunophenotype and metabolism of TCR KO donor and third-party CD19-targeted chimeric antigen receptor T cells - Abstract Relapse is the most important cause of mortality after allogeneic hematopoietic cell transplant (allo-HCT), but little research progress has been made in several decades. Chimeric antigen receptors targeting CD19 (CD19 CARs) redirect T cell effector functions to eliminate CD19-expressing leukemia and lymphoma cells. However, many patients still relapse. The candidate has preclinical data indicating the feasibility of using genome editing to delete the endogenous T cell receptor (TCR) to reduce the alloreactivity of donor CD19 CAR T cells, but it is unknown how these TCR knockout (KO) cells will function in vivo as anti-tumor agents, to what extent graft- versus-host-disease (GVHD) will result, or how engineering impacts T cell metabolism. This knowledge is essential for progress toward creating readily available “off-the-shelf” CAR T cells for patients with hematologic malignancies. The overall objectives of the proposed research are to determine how donor and third-party TCR KO CD19 CAR T cells impact immune reconstitution, GVHD, and graft rejection in preclinical models, as well as to understand how removing the TCR impacts the immunometabolism of these cells. The central hypothesis is that potent anti-tumor effects as well as negligible GVHD and graft rejection can be demonstrated preclinically by using TCR KO CD19 CAR T cells (either donor or third-party) following allo-HCT, to produce superior outcomes to conventional CD19 CAR T cells following allo-HCT. This hypothesis will be tested in the proposed Specific Aims. This work will provide ideal training for the candidate as she prepares for her long-term career goal to lead an independent laboratory studying cellular therapeutics and allo-HCT. Memorial Sloan Kettering Cancer Center has a renowned immunology program, and Dr. Marcel van den Brink, the candidate’s primary mentor, is a leader in immunotherapy research. Her co-mentor and advisory committee members have diverse and complementary expertise, and all have strong track records of mentoring independent scientists. The candidate and her mentoring team have developed a rigorous training plan designed to increase her knowledge base in: 1) development of next-generation CAR T cells; 2) bioinformatics and programming; 3) cellular metabolism, metabolic flux, mitochondrial function, and metabolic analyses in CAR T cells; and 4) professional development skills. The candidate will undertake training in these areas through coursework, workshops, and mentorship. This research project and training will provide the foundation to establish her future career as an independent physician-scientist. The proposed studies are expected to generate findings that will guide future genome engineering of CAR T cells. The candidate’s aim is to launch an independent research program designing “off- the-shelf” CAR T cells, which are expected to provide much improved therapeutic options for a range of hematologic malignancies.


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 = $167,076 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	000	5	8/21/2025	NON-COMPETING CONTINUATION	$167,076
														Subtotal = $167,076

Issue Date FY: 2024 ( Subtotal = $167,076 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	000	4	8/21/2024	NON-COMPETING CONTINUATION	$167,076
														Subtotal = $167,076

Issue Date FY: 2023 ( Subtotal = $167,076 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	000	3	8/3/2023	NON-COMPETING CONTINUATION	$167,076
														Subtotal = $167,076

Issue Date FY: 2022 ( Subtotal = $171,288 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	002	2	8/19/2022	NON-COMPETING CONTINUATION	$167,076
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	000	1	11/12/2021	NEW	$4,212
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	001	1	3/2/2022	NEW	$0
														Subtotal = $171,288

Issue Date FY: 2021 ( Subtotal = $162,864 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Blood Diseases and Resources Research	000	1	9/20/2021	NEW	$162,864
														Subtotal = $162,864

Grand Total All Awards = $835,380

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Investigating immunophenotype and metabolism of TCR KO donor and third-party CD19-targeted chimeric antigen receptor T cells

Award Number: K08HL156082

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/25/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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