A double-regulated oncolytic adenovirus with improved safety for adenocarcinoma therapy.
Safety and efficiency are equally important to be considered in developing oncolytic adenovirus. Previously, we have reported that ZD55, an oncolytic adenovirus with the deletion of E1B-55K gene, exhibited potent antitumor activity. In this study, to improve the safety of ZD55, we utilized MUC1 promoter to replace the native promoter of E1A on the basis of ZD55, and generated a double-regulated adenovirus, named MUD55. Our data demonstrated that the expression of early and late genes of MUD55 was both reduced in MUC1-negative cells, resulting in its stricter glandular-tumor selective progeny production. The cytopathic effect of MUD55 was about 10-fold lower than mono-regulated adenovirus ZD55 or Ad.MUC1 in normal cells and not obviously attenuated in glandular tumor cells. Moreover, MUD55 showed the least liver toxicity when administrated by intravenous injection in nude mice. These results indicate that MUD55 could be a promising candidate for the treatment of adenocarcinoma.
Wei
Na
N
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Fan
Jun Kai
JK
Gu
Jin Fa
JF
He
Ling Feng
LF
Tang
Wen Hao
WH
Cao
Xin
X
Liu
Xin Yuan
XY
D000230:Adenocarcinoma / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D003588:Cytopathogenic Effect, Viral; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1 / Q000235:genetics; D050130:Oncolytic Virotherapy / Q000009:adverse effects; D050504:Oncolytic Viruses / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
C060192:MUC1 protein, human; D018396:Mucin-1