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cGAS-STING Pathway Targeting Replicative Adenoviruses with CD46 Tropism and AFP Promoter Conditional Replication Restriction for the Treatment of Hepatocellular Carcinoma

Award Number: K01CA234324
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

Group Awards By Issue Date FY or Funding FY:

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ABSTRACT In the United States, hepatocellular carcinoma (HCC) is the ninth leading cause of cancer mortality, with about 30,000 new liver cancer cases diagnosed annually. HCC disproportionately affects individuals from racial/minority populations including Asian Americans, Latinos, Native Americans and African Americans. CD46 (Cluster of differentiation 46) targeting oncolytic adenoviruses (OA) represents a promising novel therapeutic platform, given their low seroprevalence and high expression of CD46 in HCC, and ease of manipulation of OA genomes. The cGAS-STING pathway represents the major immune mechanism for neutralization of DNA viruses, including OAs. I propose the development and pre-clinical evaluation of recombinant oncolytic adenoviruses with increased potency in the setting of tumor selectivity in the treatment of hepatocellular cancer. Increased potency of vectors will be achieved through targeting and inhibiting the cGAS-STING pathway. This central tenet to the project is a very high reward in nature and if successful, has the potential to have a profound impact not only in HCC research but also will have broad application pertaining to novel therapies in other cancers where oncolytic vectors can be used. The proposed research and career development plan enclosed in this application would provide additional training and mentorship to enable me to progress toward becoming an independent investigator in the field of oncolytic virotherapy for advanced liver cancer. It would also provide substantial preliminary research that will serve as the basis for an R01 application to be submitted during the final year of the K01 award.


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: 2022 ( Subtotal = $128,305 )
2022	2022	UNIVERSITY OF ARKANSAS SYSTEM	4301 W MARKHAM ST SLOT 812 BIO-MED BLDG 1 STE 102	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	002	5	8/11/2022	NON-COMPETING CONTINUATION	$128,305
2022	2021	UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES	4301 W MARKHAM ST	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	001	4	1/20/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$18,513
2022	2020	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	000	3	1/20/2022	NON-COMPETING CONTINUATION	-$18,513
														Subtotal = $128,305

Issue Date FY: 2021 ( Subtotal = $128,305 )
2021	2021	UNIVERSITY OF ARKANSAS SYSTEM	4301 W MARKHAM ST SLOT 812 BIO-MED BLDG 1 STE 102	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	002	4	9/15/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2021	UNIVERSITY OF ARKANSAS SYSTEM	4301 W MARKHAM ST SLOT 812 BIO-MED BLDG 1 STE 102	LITTLE ROCK	AR	72205	PULASKI	USA	Cancer Research Manpower	001	4	9/8/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$128,305
2021	2020	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	000	3	9/8/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $128,305

Issue Date FY: 2020 ( Subtotal = $128,305 )
2020	2020	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	000	3	8/12/2020	NON-COMPETING CONTINUATION	$128,305
														Subtotal = $128,305

Issue Date FY: 2019 ( Subtotal = $128,305 )
2019	2019	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	001	2	8/20/2019	NON-COMPETING CONTINUATION	$128,305
2019	2018	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	000	1	4/5/2019	NEW	$0
														Subtotal = $128,305

Issue Date FY: 2018 ( Subtotal = $153,850 )
2018	2018	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cancer Research Manpower	000	1	9/17/2018	NEW	$153,850
														Subtotal = $153,850

Grand Total All Awards = $667,070

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cGAS-STING Pathway Targeting Replicative Adenoviruses with CD46 Tropism and AFP Promoter Conditional Replication Restriction for the Treatment of Hepatocellular Carcinoma

Award Number: K01CA234324

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

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