REGULAR ARTICLES

Cell Research (2003); 13(6):481-489

An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy

Zi Lai ZHANG^1*, Wei Guo ZOU^1*, Chun Xia LUO¹, Bing Hua LI ¹, Jin Hui WANG¹, Lan Ying SUN¹, Qi Jun QIAN², Xin Yuan LIU^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

²Eastern Heptobiliary Hospital, Second Military Medical University, Shanghai 200438, China

^*These two authors contributed equally to this work.

Received Oct-9-2003 Revised Oct-24-2003 Accepted Nov-12-2003

Abbreviations: ZD55, recombinant adenovirus with E1B 55-kD gene deletion; NHLF, normal human lung fibroblast; MOI, multiplicity of infection; PFU, plaque-forming unit(s); CPE, cytopathic effect; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.

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.
Key words: ZD55-gene, oncolytic adenovirus, E1B 55-kD gene, cancer Gene-ViroTherapy.