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An image-guided immunotherapy and hyperthermia delivery device to overcome barriers to tumor immunity for advanced hepatocellular carcinoma

Award Number: R37CA269622
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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An image-guided immunotherapy and hyperthermia delivery device to overcome barriers to tumor immunity for advanced hepatocellular carcinoma - ABSTRACT Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related deaths in the US. Immunotherapy is a promising new treatment approach for HCC, but there are numerous barriers to immunotherapy in HCC. Local intratumoral injection of immunotherapies is a logical solution to overcoming these barriers, particularly given the fact that local immune activation can drive systemic tumor immunity. However, there are substantial gaps in knowledge regarding the intratumoral delivery of immunotherapies. When delivered through conventional needles, injected medications track along the needle path and leak out into the surrounding normal tissue. Not only does this minimize treatment efficacy due to diminished on-target delivery, but it also increases systemic toxicities. Moreover, even with local deposition of immunotherapies, persistent microenvironmental barriers can inhibit the generation of tumor immunity. This application will evaluate a novel intratumoral drug delivery system with an adjustable, electrically insulating sleeve specifically designed for intratumoral delivery of immunotherapies (ImFusion system). In addition to the controlled delivery of injected drugs, ImFusion also allows for radiofrequency-mediated intratumoral hyperthermia generation. Preliminary data show that the ImFusion system results in a substantial improvement in intratumoral drug delivery relative to conventional needles, and that its hyperthermia capabilities can “prime” the tumor microenvironment for immune activation. Our central hypothesis is not only that our ImFusion needle design will improve i.t. drug delivery, but also that the hyperthermia-mediated alterations to tumor vascularity will countervail immunologic barriers and augment i.t. immunotherapy efficacy. Accordingly, the overall objectives of this proposal are to understand how 1) variations in injection technique and thermal dose influence i.t. drug deposition, 2) hyperthermia affects tumor vascularity and immune microenvironments, and 3) hyperthermia complements i.t. immunotherapy in a syngeneic rat model of HCC. We will test our hypothesis in the following specific aims: 1) Define the influence of injection technique and hyperthermia on i.t. delivery; 2) Determine the tumor microenvironmental ramifications of hyperthermia as a function of thermal dose and time; and 3) Characterize the local and abscopal effects of hyperthermia when combined with i.t. immunotherapy. The proposal is innovative because it pursues a multimodality image-guided approach to maximize tumor immunity. In doing so, the paradigm of hyperthermia as a locoregional therapy is replaced with the paradigm of hyperthermia as an “immune primer.” The proposed research is significant because it is expected to have a broad translational impact on the efficacy of immunotherapy for patients with advanced HCC.


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 = $464,218 )
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	3	5/22/2025	NON-COMPETING CONTINUATION	$46,421
2025	2025	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	3	2/12/2025	NON-COMPETING CONTINUATION	$417,797
														Subtotal = $464,218

Issue Date FY: 2024 ( Subtotal = $446,342 )
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	2	2/8/2024	NON-COMPETING CONTINUATION	$422,851
2024	2024	THE UNIVERISTY OF TEXAS MD ANDERSON CANCER CENTER, A COMPONENT OF THE UNIVERISTY OF TEXAS SYSTEM	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	2	4/17/2024	NON-COMPETING CONTINUATION	$23,491
														Subtotal = $446,342

Issue Date FY: 2023 ( Subtotal = $460,631 )
2023	2023	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	1	3/1/2023	NEW	$460,631
														Subtotal = $460,631

Grand Total All Awards = $1,371,191

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An image-guided immunotherapy and hyperthermia delivery device to overcome barriers to tumor immunity for advanced hepatocellular carcinoma

Award Number: R37CA269622

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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