Our data indicate that vesicular stomatitis virus, VSV, is a potent agent in the eradication of malignant cells. The mechanisms underlining VSV oncolytic activity may involve flaws in the innate immune system, regulating type I interferon (IFN) production that controls the induction of anti-viral genes. We have exploited this defect by developing VSV that expresses innate immune genes such as IFN?. This virus maintains oncolytic activity in malignant cells due to existing cellular defects that prevent IFN antiviral function. However, the virus is extremely attenuated since viral produced exogenous IFN prevents viral replication in normal cells. Based on these findings, we have now generated a new VSV vectors that express IFN? as well as miR124 target sequences in the 3-UTR region of their viral genes. MiR124 is expressed in normal neuronal tissue, but not neuronal derived cancer tissue such as glioblastoma. Our preliminary data indicates that VSV-miR124-IFN is even more attenuated than VSV-IFN because prevalent miRNAs suppress viral replication in the central nervous system. The combination of using type I IFN as well as miRNAs in VSV therapeutics has led to the development of a more specific cancer virus that may be useful for the treatment of metastatic disease as well as glioblastoma. We thus propose two aims. First, we will evaluate the use of VSV-miR124-IFN as a systemic treatment against metastatic disease including melanoma and breast adenocarcinoma. Second, we will evaluate the use of VSV-miR124-IFN as a potential therapeutic to treat glioblastoma.

Public Health Relevance

Cancer is the second leading cause of death in the USA and over half a million people are expected to be diagnosed in 2014. Our research intends to test a new therapeutic agent that may be useful for the treatment of a multitude of malignant diseases, including brain cancer.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Developmental Therapeutics Study Section (DT)
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Salomon, Rachelle
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University of Miami School of Medicine
Anatomy/Cell Biology
Schools of Medicine
Coral Gables
United States
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Xia, Tianli; Konno, Hiroyasu; Ahn, Jeonghyun et al. (2016) Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis. Cell Rep 14:282-97
Ma, Zhe; Jacobs, Sarah R; West, John A et al. (2015) Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc Natl Acad Sci U S A 112:E4306-15
Barber, Glen N (2015) STING: infection, inflammation and cancer. Nat Rev Immunol 15:760-70
Ahn, J; Konno, H; Barber, G N (2015) Diverse roles of STING-dependent signaling on the development of cancer. Oncogene 34:5302-8
Betancourt, Dillon; Ramos, Juan Carlos; Barber, Glen N (2015) Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia. J Virol 89:11786-800
Kelly, Elizabeth J; Nace, Rebecca; Barber, Glen N et al. (2010) Attenuation of vesicular stomatitis virus encephalitis through microRNA targeting. J Virol 84:1550-62