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Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity

BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Korea
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Cancers 2020, 12(5), 1070; https://doi.org/10.3390/cancers12051070
Received: 8 April 2020 / Accepted: 24 April 2020 / Published: 25 April 2020
Here, we developed a novel oncolytic vaccinia virus (NOV) with the dual advantages of cancer selectivity and normal vessel reconstructive activity by replacing the viral thymidine kinase (vTk) and vaccinia growth factor (VGF) genes with genes encoding TNF-related apoptosis-inducing ligand (TRAIL) and angiopoietin 1 (Ang1), respectively. The pan-cancer-specific oncolytic potency of NOV was confirmed in various human and mouse cancer cell lines (colon, liver, pancreas, cholangiocarcinoma, cervical cancer, osteosarcoma, and melanoma). Vaccinia virus (VV) treatment directly induced early apoptosis in tumors within 24 h, and this effect was enhanced with further engineering; VGF and Tk deletion with Ang1 and TRAIL insertion. Meanwhile, treatment with the conventional anti-cancer drug cisplatin did not induce apoptosis. A virus-treated CT26 mouse colon cancer syngeneic model showed attenuated tumor growth, which was in accordance with the results of percent survival measurement, CD8 expression analysis, and TUNEL staining with advanced genetic engineering (vAng1 < vTRAIL < NOV). Taken together, our results indicate that NOV induces cancer tissue apoptosis and anti-tumor immunity and may constitute a highly advantageous therapeutic agent for next-generation solid tumor virotherapy with pan-cancer-specific oncolytic activity and high biosafety. View Full-Text
Keywords: oncolytic virus; angiopoietin 1; TRAIL oncolytic virus; angiopoietin 1; TRAIL
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Jeong, S.-N.; Yoo, S.Y. Novel Oncolytic Virus Armed with Cancer Suicide Gene and Normal Vasculogenic Gene for Improved Anti-Tumor Activity. Cancers 2020, 12, 1070.

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