Potent anti-tumor activity of telomerase-dependent and HSV-TK armed oncolytic adenovirus for non-small cell lung cancer in vitro and in vivo

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality, any improvements in therapeutic strategies are urgently required. In this study we generated a novel 'suicide gene' armed oncolytic adenoviral vector and investigated its antitumor effect both in vitro and in vivo. Methods: Since the up-regulated expression of human telomerase reverse transcriptase (hTERT) is a hallmark of alltypes of NSCLC, we chose hTERT promoter to transcriptionally control E1A gene expression to obtain adenoviral replication in NSCLC. In order to further enhance anti-tumor effect of this oncolytic adenoviral vector, we inserted a 'suicide gene' i.e. Herpes Simplex Virus Thymidine Kinase (HSV-TK) into oncolytic adenoviral vector to engineer a novel armed oncolytic adenoviral vector 'Ad.hTERT-E1A-TK'. Results: Ad. hTERT-E1A-TK efficiently killed different types of tumor cells including two types of NSCLC cells in vitro, causing no damage to normal primary fibroblasts. Furthermore, Ad. hTERT-E1A-TK infection combined with administration of prodrug gancyclovir (GCV) resulted in more potent cytotoxicity on NSCLC cells, and synergistically suppressed human NSCLC tumor growth in nude mice. Conclusion: The results from this study showed that Ad. hTERT-E1A-TK/GCV could be a potent but safe anti-tumor strategy for NSCLC biotherapy.