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Development of novel AAV vaccine strategy in a pre-clinical model of oral melanoma.

Award Number: R01CA285620
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/08/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2028

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Development of novel AAV vaccine strategy in a pre-clinical model of oral melanoma. - Project Summary/Abstract Vaccination is a potent regulator of the immune system and much research is being conducted to understand how antigen-specific stimulation can be used to induce and redirect anti-tumor immunity. Our team develops a cancer immunotherapy program using novel AAV vectors to deliver antigens both directly and by cross- presentation to antigen presenting cells. Optimization of naturally occurring AAV serotypes and novel methods of AAV production are necessary to warrant wide use of these vectors for cancer immunotherapy. The main aims of this proposal is to determine the safety and efficacy of our novel AAV-based vaccines as part of preclinical studies by using companion dogs with oral melanoma. In recent years, we have undertaken studies to gain a better understanding of the underlying molecular mechanisms of AAV and host immune system interaction via the high efficiency transduction of DCs. We have made the following scientific achievements, which form the basis of the current proposal: • Identified and mutagenized critical surface-exposed serine and threonine residues on the AAV capsid that are involved in intracellular trafficking of virus in the host cells. • Demonstrated that rational modifications in the AAV expression cassette results in antigen processing by dendritic cells (DCs), leading to a stronger and prolonged antigen-specific immune response. • Developed the next generation of highly efficient AAV-vectors that expressed a tumor-associated antigens (premelanosome protein gp100 (also known as Pmel), tyrosinase (Tyr), tyrosinase-related protein 1(TRP1), and dopachrome tautomerase (TRP2). • Tested these novel AAV vectors for their ability to stimulate a specific T-cell clone proliferation and protective immune response in a small animal model. In this proposal, we will test ability of our recently developed optimized AAV capsid and expression cassette, whose unique properties enhance a cellular/humoral immune response toward vector encoded tumor antigens. Successful completion of the current proposal will result in: • Production of high titers of a therapeutic AAV-based vaccine. • Identification of an optimal AAV-based dose for vaccination that can be used to slow/eliminate the progression of melanoma cancer in a large animal model such as companion dog-patients with spontaneous cancer. • Mechanism of the novel cancer vaccine function in the most appropriate animal model. The optimized AAV vector can be potentially used as a vaccine platform for the treatment of cancers in canine and humans.


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 = $485,977 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Cancer Treatment Research	001	3	4/17/2026	NON-COMPETING CONTINUATION	$48,598
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Cancer Treatment Research	000	3	12/11/2025	NON-COMPETING CONTINUATION	$437,379
														Subtotal = $485,977

Issue Date FY: 2025 ( Subtotal = $488,155 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Cancer Treatment Research	000	2	11/13/2024	NON-COMPETING CONTINUATION	$439,339
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Cancer Treatment Research	001	2	7/2/2025	NON-COMPETING CONTINUATION	$48,816
														Subtotal = $488,155

Issue Date FY: 2024 ( Subtotal = $503,863 )
2024	2024	REGENTS OF THE UNIVERSITY OF MINNESOTA	200 OAK ST SE	MINNEAPOLIS	MN	55455	HENNEPIN	USA	Cancer Treatment Research	000	1	12/8/2023	NEW	$503,863
														Subtotal = $503,863

Grand Total All Awards = $1,477,995

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Development of novel AAV vaccine strategy in a pre-clinical model of oral melanoma.

Award Number: R01CA285620

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/08/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2028

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