Cancer Targeting Gene-Viro-Therapy of Liver Carcinoma by Dual-regulated Oncolytic Adenovirus Armed with TRAIL Gene

A team of researchers, led by LIU Xin-Yuan at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, developed a novel therapeutic strategy for cancer treatment named ‘Cancer Targeting Gene-Viro-Therapy’ (CTGVT).

 

Although major progress has been made in the field of cancer therapy in the past decades, liver cancer remains one of the most refractory malignancies. Novel therapeutic methods with high effectiveness and safety are urgently needed. CAO Xin and his colleagues, based on an E1B-55K-deleted construct, ZD55, replaced the native viral E1A promoter with the simian virus 40 (SV40) enhanced α-fetoprotein (AFP) promoter as enAFP and constructed a dual-regulated oncolytic adenoviral vector designated Ad•AFP•E1A•E1B (Δ55) (briefly Ad•AFP•D55). Ad•AFP•D55 showed specific replication and cytotoxicity in AFP-positive hepatoma cells. It also demonstrated enhanced safety in normal cells when compared to the mono-regulated vector ZD55. To improve the anti-hepatoma activities of the virus, the tumor necrosis factor­related apoptosis­inducing ligand (TRAIL) gene was introduced into Ad•AFP•D55. Ad•AFP•D55-TRAIL exhibited remarkable anti-tumor activities in vitro and in vivo. Treatment with Ad•AFP•D55-TRAIL can induce both autophagy due to the Ad•AFP•D55 vector and caspase-dependent apoptosis due to the TRAIL protein. The CTGVT has excellent antitumor effects due to that the oncolytic virus can target and replicate in cancer cells with several hundred to several thousand folds, thus the inserted genes can also be amplified at the same magnitude, then the resulting CTGVT virus show much better excellent antitumor effect not only in vitro but also in vivo than that of either gene therapy alone or virotherapy alone. Therefore, CTGVT has been considered as a new trend in both gene therapy and virotherapy for cancer therapy.

 

This study entitled ‘Cancer Targeting Gene-Viro-Therapy of Liver Carcinoma by Dual-regulated Oncolytic Adenovirus Armed with TRAIL Gene’ was published online in Gene Therapy on March 17^th, 2011.

 

This work was supported by the grants from the National Basic Research Program of China (973 Program), the Hi-Tech Research Development Program of China (863 Program), the National Natural Science Foundation of China, the Key Project of the Chinese Academy of Sciences, and the Science and Technology Commission of Shanghai Municipality. (SIBCB) .

 

AUTHOR CONTACT:

LIU Xin-Yuan

Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

Phone: 86.21.54921126; E-mail: xyliu@sibs.ac.cn