The ultimate goal of this proposal is to understand the contribution of Vstat120 expressing oncolytic viruses on OV propagation, tumor biology and anti-tumor efficacy. These results will lead to a better understanding of OV therapy induced changes in tumor biology and will lead to the development of a dually armed cancer killing OV. The OV treatment of tumors relies on cancer-specific replication of the virus leading to tumor destruction with minimal toxicity to adjacent non-neoplastic tissue. Results from six clinical trials using replication competent OVs to treat patients with malignant glioma have shown the new modality to be relatively safe, but high expectations of efficacy remain unmet (1, 2). The tumor's microenvironment is increasingly recognized as an important determinant for its progression and its response to therapeutics. My laboratory has recently created two oncolytic viruses, armed with an anti-angiogenic gene. We now propose to elucidate the role of this angiostatic protein in viral propagation, glioma biology and OV efficacy.
The American Cancer Society predicts that there will be 12,740 deaths due to cancers of the brain/nervous system. Despite decades of research prognosis for patients suffering from malignant gliomas remains poor. Oncolytic viral therapy is an experimental treatment which is currently being evaluated in clinical trials for efficacy against brain tumors. The proposed research outlined in this grant is highly significant because it will elucidate the impact of an oncolytic virus armed with Vstat120 on tumor microenvironment, and OV efficacy. The results will help translate oncolytic viral therapy into an efficacious treatment for tumors.
|Yoo, Ji Young; Jaime-Ramirez, Alena Cristina; Bolyard, Chelsea et al. (2016) Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy. Clin Cancer Res 22:5265-5276|
|Ru, Peng; Hu, Peng; Geng, Feng et al. (2016) Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth. Cell Rep 16:1527-35|
|Lee, Tae Jin; Haque, Farzin; Shu, Dan et al. (2015) RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model. Oncotarget 6:14766-76|
|Cheng, Chunming; Ru, Peng; Geng, Feng et al. (2015) Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth. Cancer Cell 28:569-81|
|Lee, Tae Jin; Haque, Farzin; Vieweger, Mario et al. (2015) Functional assays for specific targeting and delivery of RNA nanoparticles to brain tumor. Methods Mol Biol 1297:137-52|
|Han, Jianfeng; Chen, Xilin; Chu, Jianhong et al. (2015) TGFÎ² Treatment Enhances Glioblastoma Virotherapy by Inhibiting the Innate Immune Response. Cancer Res 75:5273-82|
|Yoo, Ji Young; Yu, Jun-Ge; Kaka, Azeem et al. (2015) ATN-224 enhances antitumor efficacy of oncolytic herpes virus against both local and metastatic head and neck squamous cell carcinoma. Mol Ther Oncolytics 2:15008|
|Meisen, W Hans; Wohleb, Eric S; Jaime-Ramirez, Alena Cristina et al. (2015) The Impact of Macrophage- and Microglia-Secreted TNFÎ± on Oncolytic HSV-1 Therapy in the Glioblastoma Tumor Microenvironment. Clin Cancer Res 21:3274-85|
|Meisen, Walter Hans; Dubin, Samuel; Sizemore, Steven T et al. (2015) Changes in BAI1 and nestin expression are prognostic indicators for survival and metastases in breast cancer and provide opportunities for dual targeted therapies. Mol Cancer Ther 14:307-14|
|Jacobsen, Karly; Russell, Luke; Kaur, Balveen et al. (2015) Effects of CCN1 and Macrophage Content on Glioma Virotherapy: A Mathematical Model. Bull Math Biol 77:984-1012|
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