Abstract
Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector, in which the hTERT promoter element drives expression of E1 genes, OBP-301 (Telomelysin). Since only tumor cells that express telomerase activity would 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. OBP-301 alone exhibited substantial antitumor effects both in animal models and in clinical trials; data regarding combination therapy with OBP-301 and chemotherapeutic agents are preliminary but encouraging. This article reviews synergistic interaction of virotherapy and chemotherapy, and illustrates the potential application for the treatment of human cancer.
Keywords: Telomerase, adenovirus, virotherapy, docetaxel, histon deacetylase inhibitor, gemcitabine, neoplastic disease, viral genes
Current Pharmaceutical Biotechnology
Title:Synergistic Interaction of Telomerase-Specific Oncolytic Virotherapy and Chemotherapeutic Agents for Human Cancer
Volume: 13 Issue: 9
Author(s): Toshiyoshi Fujiwara, Shunsuke Kagawa and Hiroshi Tazawa
Affiliation:
Keywords: Telomerase, adenovirus, virotherapy, docetaxel, histon deacetylase inhibitor, gemcitabine, neoplastic disease, viral genes
Abstract: Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector, in which the hTERT promoter element drives expression of E1 genes, OBP-301 (Telomelysin). Since only tumor cells that express telomerase activity would 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. OBP-301 alone exhibited substantial antitumor effects both in animal models and in clinical trials; data regarding combination therapy with OBP-301 and chemotherapeutic agents are preliminary but encouraging. This article reviews synergistic interaction of virotherapy and chemotherapy, and illustrates the potential application for the treatment of human cancer.
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Cite this article as:
Fujiwara Toshiyoshi, Kagawa Shunsuke and Tazawa Hiroshi, Synergistic Interaction of Telomerase-Specific Oncolytic Virotherapy and Chemotherapeutic Agents for Human Cancer, Current Pharmaceutical Biotechnology 2012; 13 (9) . https://dx.doi.org/10.2174/138920112800958887
DOI https://dx.doi.org/10.2174/138920112800958887 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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