Multidisciplinary cancer therapy with telomerase-specific oncolytic adenovirus

Research output: Contribution to journalArticle

Abstract

A multidisciplinary approach of combining surgery, chemotherapy and radiotherapy has remained the accepted standard management for various types of human cancer. However, many new treatment options have recently become available, including molecular targeted therapies, immunotherapies and oncolytic virotherapies. Replication-selective tu-mor-specific viruses have been designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. We constructed an attenuated adenovirus 5 vector, telomelysin (OBP-301), in which the telomerase-specific promoter drives expression of viral replication-inducible E1 genes. Although telomelysin alone exhibited substantial antitumor effects both in animal models and in clinical trials, telomelysin has the potential to be the first-in-class oncolytic virus for combination therapy based on our current understanding of the molecular mechanisms. Telomelysin sensitizes human cancer cells to ionizing radiation by inhibiting the radiation-induced DNA repair machinery, and also eliminates radio-resistant quiescent cancer stem-like cells by promoting cell cycle entry. A clinical trial of intratumoral administration of telomelysin with radiotherapy in esophageal cancer patients is currently underway. This article reviews recent highlights in the rapidly evolving field of multidisciplinary therapy with telomelysin.

Original languageEnglish
Pages (from-to)178-187
Number of pages10
JournalCurrent Cancer Therapy Reviews
Volume11
Issue number3
DOIs
Publication statusPublished - Jan 1 2015

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Telomerase
Adenoviridae
Oncolytic Virotherapy
Neoplasms
Radiotherapy
Clinical Trials
Molecular Targeted Therapy
Viruses
Neoplastic Stem Cells
Therapeutics
Esophageal Neoplasms
Ionizing Radiation
Radio
DNA Repair
Immunotherapy
Cell Cycle
Animal Models
Radiation
Drug Therapy
Genes

Keywords

  • Adenovirus
  • Cancer stem cells
  • DNA repair
  • Radiotherapy
  • Telomerase

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

Cite this

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