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.
