[Oncolytic virotherapy for human solid tumors].
Replication-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 with a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field of cancer therapeutic and diagnostic approaches using telomerase-specific oncolytic adenoviruses.
Fujiwara
Toshiyoshi
T
Center for Gene and Cell Therapy, Okayama University Hospital, Okayama, Japan.
D000256:Adenoviridae / Q000235:genetics; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000628:therapy* / Q000821:virology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D013379:Substrate Specificity; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
D019098:Telomerase