An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy |
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Authors: | Zhang Zi Lai Zou Wei Guo Luo Chun Xia Li Bing Hua Wang Jin Hui Sun Lan Ying Qian Qi Jun Liu Xin Yuan |
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Institution: | Laboratory of Biotechnology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. |
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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 ElB 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. |
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Keywords: | ZD55-gene oncolytic adenovirus ElB 55-kD gene cancer Gene-ViroTherapy |
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