Tuesday, September 16, 2025 9/16/2025

Development of murine glioblastoma model for oncolytic HSV therapy

Award Number: R61NS128191
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/09/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Development of murine glioblastoma model for oncolytic HSV therapy - The overall goal of this project is to create a murine-models for grade IV brain tumors that will be sensitive to HSV-1 infection and can be utilized to evaluate oncolytic HSV-1 (oHSV) derived viruses utility and safety for grade IV brain tumors. Grade IV primary brain tumors are associated with a very poor prognosis, and despite surgery and use of chemotherapy, radiotherapy and tumor treating field delivering devices patient survival remains dismal. Hence there is an urgent need for alternative therapies. Oncolytic HSV-1 based viral therapy (oHSV) is a promising biological therapy for solid tumor. oHSV is currently approved for treatment of metastatic melanoma in USA and Europe. Another oHSV recently was given conditional approval for treatment of recurrent GBM in Japan. Several oHSV are currently being investigated for safety and efficiency for brain tumors include G207, HSV1716, M032 and rQuestin34.5. Additional development of novel and second-generation viruses is also actively being pursued in many laboratories. However, the species-specific nature of virus and host interactions presents a challenge in currently available murine models. Thus a mouse model that is immune competent, produces reproducible tumors, and is permissive to HSV-1 would help expedite safety and efficacy testing of this new and promising biotherapy. An animal model that is immune competent, permissive to HSV-1, not overly immunogenic, and shows reproducible and efficient tumor growth would be ideal to test oHSV based biotherapies. Here we propose to create an animal model recapitulates the effect of HSV-1 on tumor cells and the immune environment but still has an ECM environment consisting of microglia, endothelial cells etc. that are also permissive. A syngeneic murine GBM model, that is permissive to HSV-1 infection without being overly immunogenic and shows a 100% tumor take in mice upon transplantation would be ideal. We have created transgenic mice that express human Nectin-1 to permit efficient virus entry. We will use NSC from these mice to create brain tumor cells that mimic human brain tumor genetic alterations and evaluate them for tumor take and response to oHSV therapy.


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 = $375,155 )
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/10/2025	NON-COMPETING CONTINUATION	$375,155
														Subtotal = $375,155

Issue Date FY: 2024 ( Subtotal = $395,812 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/9/2024	NEW	$399,155
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/16/2024	NEW	-$3,343
														Subtotal = $395,812

Grand Total All Awards = $770,967

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Development of murine glioblastoma model for oncolytic HSV therapy

Award Number: R61NS128191

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/09/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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