ID 57472
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Author
Fujiwara, Toshiyoshi Department of Gastroenterological Surgery Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kakenhi
Abstract
Replication-selective tumor-specific viruses represent a novel approach for treating neoplastic diseases. These vectors are designed to induce virus-mediated lysis of tumor cells after selective intracellular virus propagation. For targeting cancer cells, the use of tissue- or cell-specific promoters that are expressed in diverse tumor types but silent in normal cells is required. Human telomerase is highly active in more than 85% of primary cancers, regardless of tissue origin, and its activity is closely correlated 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. As only tumor cells that express the telomerase can activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death. Upon US Food and Drug Administration approval, a phase 1 dose-escalation study of intratumoral injection of telomelysin for various solid tumors has been completed to confirm the safety, tolerability, and feasibility of the agent. Moreover, we found that adenoviral E1B 55-kDa protein in telomelysin inhibits the radiation-induced DNA repair machinery. Thus, tumor cells infected with telomelysin could be rendered sensitive to ionizing radiation. Recently, we assessed the safety and efficacy of intratumoral injection of telomelysin with radiotherapy in esophageal cancer patients not suited for standard treatments. This review highlights some very promising clinical advances in cancer therapeutic technologies using telomerase-specific oncolytic virotherapy.
Keywords
adenovirus
clinical trial
esophageal cancer
radiotherapy
telomerase
Published Date
2019-07-05
Publication Title
Annals of gastroenterological surgery
Volume
volume3
Issue
issue4
Publisher
John Wiley & Sons
Start Page
396
End Page
404
ISSN
24750328
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2019 The Authors
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DOI
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isVersionOf https://doi.org/10.1002/ags3.12270
License
http://creativecommons.org/licenses/by-nc-nd/4.0/