Synergistic interaction of telomerase-specific oncolytic virotherapy and chemotherapeutic agents for human cancer

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7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1809-1816
Number of pages8
JournalCurrent Pharmaceutical Biotechnology
Volume13
Issue number9
DOIs
Publication statusPublished - Jul 2012

Keywords

  • Adenovirus
  • Docetaxel
  • Gemcitabine
  • Histon deacetylase inhibitor
  • Telomerase
  • Virotherapy

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

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