Targeted Oncolytic Adenovirus for Human Cancer Therapy: Gene-Based Therapies for Cancer

Abstract

Replication-selective tumor-specific viruses represent a novel approach for the treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. For targeting cancer cells, there is a need for tissue- or cell-specific promoters that are expressed in diverse tumor types, but are silent in normal cells. Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector, in which the hTERT promoter element drives the expression of E1 genes. As only tumor cells that express telomerase activity activate this promoter, the hTERT proximal promoter allows for a preferential expression of viral genes in tumor cells, leading to selective viral replication and oncolytic cell death. This article reviews the recent findings in this rapidly evolving field; cancer therapeutic and cancer diagnostic approaches using the hTERT promoter.