A Prostate Cancer-Specific Targeting Gene-Viro-Therapy with Double Regulated Oncolytic Virus Harboring PTEN Gene
Source:
Time: 2012-05-08
Prostate cancer is a major health problem for men in Western societies. Recently, a team of researchers, led by Prof. LIU Xinyuan, at Shanghai Institute of Biochemistry and Cell Biology, CAS, developed a novel Cancer-specific Targeting Gene-Viro-Therapy with prostate cancer-specific antitumor effect, which was published online in PloS One on April 11th, 2012.
The Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa) was developed by DING Miao and her colleagues, in which PTEN was inserted into a DD3-controlled oncolytic viral vector to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) (briefly, Ad.DD3.D55-PTEN). The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence to enhance the expression level of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN has prostate cancer specific antitumor effect. The CTGVT-PCa construct reported here killed all of the prostate cancer cell lines tested, such as DU145, 22RV1 and CL1, but had a reduced or no killing effect on all the non-prostate cancer cell lines tested. The tumor growth rate was almost completedly inhibited after Ad.DD3.D55-PTEN treatment, which showing the powerful antitumor effect of Ad.DD3.D55-PTEN on prostate cancer tumor growth. The CTGVT-PCa 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-PCa virus show much better antitumor effect not only in vitro but also in vivo than that of either gene therapy alone or virotherapy alone. Therefore, CTGVT-PCa has been considered as a new trend in both gene therapy and virotherapy for prostate cancer therapy.
This work was supported by the National Basic Research Program of China, Important National Science &Technology Specific Project, New Innovation Program, the Zhejiang Sci-Tech University grant, and grant from the Science and Technology Commission of Shanghai Municipality.
AUTHOR CONTACT:
LIU Xinyuan
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China
Cancer-specific Targeting Gene-Viro-Therapy with prostate cancer-specific antitumor effect. Crystal violet staining showed Prostate cancer-specific cytotoxicity of Ad.DD3.D55-PTEN in vitro. (Image Provided by Dr.LIU Xinyuan)
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