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Functional epigenomics of transgenic cellular immunotherapies for cancer

Award Number: K08CA241088
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/10/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Functional epigenomics of transgenic cellular immunotherapies for cancer - PROJECT SUMMARY/ABSTRACT Cancer immunotherapy with T-cells expressing a transgenic T-cell receptor (TCR) can generate sustained clinical responses in a variety of malignancies. However, many patients do not respond, or eventually relapse. The goals of this proposal are to classify how progressive epigenomic and transcriptomic changes experienced by clinical transgenic TCR T-cells over time are associated with a gradual loss of function of these therapies, and how these changes correlate with clinical response or non-response to therapy. The proposed research focuses on the comparison of the epigenomic, transcriptomic, phenotypic, and functional characteristics of baseline transgenic TCR T-cells with samples recovered at later timepoints, utilizing a large cohort of clinical samples from patients treated with these cell therapeutics. In doing so, the candidate will address three main research aims: 1) Relate the epigenomic/transcriptomic changes experienced by transgenic T-cells over time, and their T-cell-specific in silico ontological/functional associations, with clinical response to therapy; 2) Define the transgenic T-cells’ progressive changes in phenotypic and cytokine secretion functionality profiles associated with clinical response or non-response to therapy; and 3) Determine the impact of epigenetic silencing on suppression of the expression of the transgenic TCR itself over time. The practical implications of this work include the enabling of highly detailed epigenomic profiling of a given patient’s transgenic T-cell therapeutics to help guide clinical decision-making, as well as provide novel targets for genetic engineering of newer generations of transgenic cellular therapies. The candidate is firmly committed to a career in translational cellular immunotherapy research, and is strongly supported in his career and research goals by his mentors and his department/division at the University of California, Los Angeles. He currently holds a position as a Clinical Instructor in the Department of Pediatrics, Division of Pediatric Hematology/Oncology, with 80% protected time for research. The current proposal builds on the candidate’s previous research and clinical experience by including a comprehensive mentorship and didactic plan to advance the candidate’s skills and knowledge in epigenomics and computational biology required for developing expertise in this area of focus. Under the guidance of his primary mentor, Dr. Antoni Ribas, and his Scientific Advisory Committee members Dr. Theodore Moore, Dr. Matteo Pellegrini, and Dr. Yvonne Chen, he will advance his bioinformatics skills, while learning epigenomic, T-cell phenotype profiling, and cytokinetic functionality methodologies that will be directly applied to this proposal. Completion of this comprehensive training and research plan will provide the candidate with the skills and experience necessary to become a successful independent investigator specializing in cellular immunotherapies for the treatment of cancer, with a focus on the cells’ epigenomic changes over time and their correlates with clinical response to therapy.


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 = $181,886 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	000	5	1/15/2025	NON-COMPETING CONTINUATION	$181,886
														Subtotal = $181,886

Issue Date FY: 2024 ( Subtotal = $181,886 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	000	4	1/23/2024	NON-COMPETING CONTINUATION	$181,886
														Subtotal = $181,886

Issue Date FY: 2023 ( Subtotal = $181,886 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	000	3	1/12/2023	NON-COMPETING CONTINUATION	$181,886
														Subtotal = $181,886

Issue Date FY: 2022 ( Subtotal = $181,886 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cancer Research Manpower	000	2	1/31/2022	NON-COMPETING CONTINUATION	$181,886
														Subtotal = $181,886

Issue Date FY: 2021 ( Subtotal = $181,886 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cancer Research Manpower	000	1	2/10/2021	NEW	$181,886
														Subtotal = $181,886

Grand Total All Awards = $909,430

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Functional epigenomics of transgenic cellular immunotherapies for cancer

Award Number: K08CA241088

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/10/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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