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Exosome-mediated therapy for liver cancer

Award Number: R21CA280232
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/12/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Exosome-mediated therapy for liver cancer - Hepatocellular carcinoma (HCC) is the most common primary liver cancer that represents the second most common cause of cancer-related death worldwide. In addition, the liver the most common site for metastatic cancer. Transarterial chemo- or radio-embolization (TACE/TARE) for unresectable HCC exploits the hepatic tumors’ blood supply via the hepatic artery to selectively deliver the embolic agents and therapeutics into targeted region of the liver. However, these treatments are largely palliative and direct visualization of the delivery after contrast washout is not possible. Thus, new theranostic modalities are urgently needed. Alpha- emitting radiopharmaceutical therapy (αRPT) is emerging as a highly potent treatment that effectively targets single cells, minimal residual disease, and micrometastatic lesions to eradicate cancer cells that exhibit resistance to conventional treatment. To address diffusion-limited penetration depths of αRPT that may result in partial tumor irradiation, we propose to develop a dual modality imaging-visible, exosome-mediated radiotheranostic platform for an alpha emitter delivery. In Specific Aim 1, we will evaluate the imaging visibility and targeting ability of radiolabeled exosomes in cell monolayers and 3D vascularized spheroids. A selected αRPT formulation will be tested in ectopic and orthotopic HCC mouse models (Aim 2), allowing us to evaluate its biodistribution, efficacy and safety via intratumoral and intraarterial delivery. The proposed study brings a unique combination of expertise in radiosynthesis, dosimetry, medical imaging, and animal model of cancers, to address the critical challenges for effective HCC treatment. Successful completion of the proposed activities will have vast ramifications for advancing the development of exosome-mediated αRPT for treating HCC or other cancers.


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 = $113,465 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	000	3	12/22/2025	NON-COMPETING CONTINUATION	$113,465
														Subtotal = $113,465

Issue Date FY: 2025 ( Subtotal = $65,311 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	000	2	2/13/2025	NON-COMPETING CONTINUATION	$46,173
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	001	2	5/23/2025	NON-COMPETING CONTINUATION	$19,138
														Subtotal = $65,311

Issue Date FY: 2024 ( Subtotal = $229,659 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	000	1	1/12/2024	NEW	$229,659
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Treatment Research	001	1	2/21/2024	NEW	$0
														Subtotal = $229,659

Grand Total All Awards = $408,435

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Exosome-mediated therapy for liver cancer

Award Number: R21CA280232

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/12/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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