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 tumor-
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.
Keywords: Adenovirus, cancer stem cells, DNA repair, radiotherapy, telomerase.
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