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Engineered T cell-based imaging for glioblastoma and CAR-T cell tracking

Award Number: R01CA271602
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/21/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Engineered T cell-based imaging for glioblastoma and CAR-T cell tracking - Molecular biology, genomics, and immunology are revolutionizing modern medicine by uncovering key molecular markers in human diseases. Imaging technologies that can directly visualize these markers, such as immune- positron emission tomography (immunoPET), are at the forefront of such innovation, reshaping current medical practice. In this proposal, we take advantage of both the superior targeting specificity of monoclonal antibodies (mAb), and the amplification inherent in cell signaling by developing a T cell-based imaging method. Using synthetic biology, we will develop engineered T cells with an antibody-derived chimeric receptor called “SNIPR” that has an antigen-recognizing single-chain variable fragment (scFv) as an extracellular domain and an engineered transcription factor as an intracellular domain. Upon binding its target antigen, SNIPR releases its transcription factor, which migrates into the nucleus and induces the overexpression of various exogenous reporter gene(s). This approach is fully customizable and versatile, and most importantly, can greatly enhance sensitivity through multiple rounds of signal amplifications. The main goals of this proposal are to establish the preclinical groundwork for SNIPR-PET in (1) visualizing early glioblastoma and (2) tracking activated CAR T cells. In Aim 1, we will refine SNIPR T cells targeting EGFRvIII and optimize SNIPR-PET reporter imaging strategies. In Aim 2, we will apply SNIPR-PET to the molecular imaging of glioblastoma and compare its sensitivity and specificity with antibody-based immunoPET. In Aim 3, we will image CD8+ therapeutic T cells, establish a correlation between PET signals and tumor response, and enhance T cell penetration into brain tissues. The developed technologies will allow non-invasive monitoring of biological/immunological responses within tumors, as potential biomarkers of successful therapy. This collaborative proposal between Immunology, Radiology and Neurosurgery will provide a versatile and customizable tool allowing cancer detection and treatment using engineered T cells. Our proposal reflects a close interdisciplinary collaboration between Drs. Kole Roybal, (Immunology), David Wilson (Radiology), and Hideho Okada (Neuroradiologic Surgery) at UCSF. Dr. Jaehoon Shin, an interventional radiologist and molecular biologist, is another primary driver of this project- integrating molecular biology, genomics, synthetic biology and biomedical imaging. We believe that our successful execution of the proposed work will greatly impact human health by introducing novel T cell-based imaging to detect early cancers and to enhance the safety profile of therapeutic T cells.


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 = $659,959 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	4	8/13/2026	NON-COMPETING CONTINUATION	$659,959
														Subtotal = $659,959

Issue Date FY: 2025 ( Subtotal = $659,855 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	3	9/11/2025	NON-COMPETING CONTINUATION	$659,855
														Subtotal = $659,855

Issue Date FY: 2024 ( Subtotal = $626,733 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	2	7/22/2024	NON-COMPETING CONTINUATION	$626,733
														Subtotal = $626,733

Issue Date FY: 2023 ( Subtotal = $659,642 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Detection and Diagnosis Research	000	1	9/21/2023	NEW	$659,642
														Subtotal = $659,642

Grand Total All Awards = $2,606,189

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Engineered T cell-based imaging for glioblastoma and CAR-T cell tracking

Award Number: R01CA271602

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/21/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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