1. ¹Laboratory of Biotechnology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. E-mail: xyliu@sibs.ac.cn
2. ²Eastern Heptobiliary Hospital, Second Military Medical University, Shanghai 200438, China

Correspondence: Prof. Xin Yuan LIU, Tel: 86-21-64746126; Fax: 86-21-64746126; E-mail: xyliu@sibs.ac.cn

^*These two authors contributed equally to this work.

Received 9 October 2003; Revised 24 October 2003; Accepted 12 November 2003.

Abstract

ONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them. To date, clinical trials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone. In this paper, we put forward a novel concept of Gene-ViroTherapy strategy and in this way, we constructed an armed therapeutic oncolytic adenovirus system, ZD55-gene, which is not only deleted of E1B 55-kD gene similar to ONYX-015, but also armed with foreign antitumor gene. ZD55-gene exhibited similar cytopathic effects and replication kinetics to that of ONYX-015 in vitro. Importantly, the carried gene is expressed and the expression level can increase with the replication of virus. Consequently, a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer. Our data demonstrated that ZD55-gene, which utilizing the Gene-ViroTherapy strategy, is more efficacious than each individual component in vivo.