Significant antitumor activity of oncolytic adenovirus expressing human interferon-beta for hepatocellular carcinoma.
BACKGROUND
Human interferon-beta (IFN-beta) has been widely used in gene therapy for its antitumor activity but its therapeutic effect is limited. The conditionally replicative adenovirus ONYX-015 (a E1B-55-kDa-deleted adenovirus) targets well to tumor cells, but is not potent enough to cause significant tumor regression. To solve these problems, a tumor-selective replicating adenovirus expressing IFN-beta was constructed in this study.


METHODS
The oncolytic adenoviruses were generated by homologous recombination in packaging cells. The expression of the IFN-beta protein was detected by enzyme-linked immunosorbent assay (ELISA). The antitumor efficacy of ZD55-IFN-beta was evaluated in cell lines and human hepatocellular carcinoma xenografts in nude mice.


RESULTS
ZD55-IFN-beta can express much more IFN-beta than Ad-IFN-beta because of the replication of the ZD55 vector. Our data showed that ZD55-IFN-beta could exert a strong cytopathic effect on tumor cells (about 100-fold higher than Ad-IFN-beta or ONYX-015). Moreover, no obvious cytotoxic or apoptotic effects were detected in normal cells infected with ZD55-IFN-beta.


CONCLUSIONS
The antitumor efficacy of IFN-beta could be significantly improved due to the increased gene expression level from the tumor-selective replicating vector. The oncolytic adenovirus expressing IFN-beta may provide a novel approach for cancer gene therapy.
He
Ling Feng
LF
Laboratory of Cancer Therapy, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Gu
Jin Fa
JF
Tang
Wen Hao
WH
Fan
Jun Kai
JK
Wei
Na
N
Zou
Wei Guo
WG
Zhang
Yan Hong
YH
Zhao
Li Li
LL
Liu
Xin Yuan
XY
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017930:Genes, Reporter; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D014765:Viral Vaccines; D023041:Xenograft Model Antitumor Assays
D014765:Viral Vaccines; C464532:dl1520; D016899:Interferon-beta