An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy.
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.
Zhang
Zi Lai
ZL
Laboratory of Biotechnology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zou
Wei Guo
WG
Luo
Chun Xia
CX
Li
Bing Hua
BH
Wang
Jin Hui
JH
Sun
Lan Ying
LY
Qian
Qi Jun
QJ
Liu
Xin Yuan
XY
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009857:Oncogenes / Q000187:drug effects*; D014183:Transplantation, Heterologous; D014779:Virus Replication
D000970:Antineoplastic Agents; D005472:Fluorouracil