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Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter Fujiwara T; Tanaka NUirusu 2008[Jun]; 58 (1): 11-8Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.|*Adenoviridae/genetics[MESH]|*Oncolytic Virotherapy/methods[MESH]|*Promoter Regions, Genetic[MESH]|*Telomerase/genetics/metabolism[MESH]|Adenovirus E1 Proteins[MESH]|Animals[MESH]|Clinical Trials, Phase I as Topic[MESH]|Genetic Vectors/*therapeutic use[MESH]|Green Fluorescent Proteins/genetics[MESH]|Humans[MESH]|Mice[MESH]|Neoplasms/diagnosis/*therapy[MESH] |
