A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent

Zou, Weiguo; Luo, Chunxia; Zhang, Zilai; Liu, Jing; Gu, Jianying; Zhang, Pei; Qian, Cheng; Liu, Xinyuan

doi:10.1038/sj.onc.1207033

Cited by 58 publications

(45 citation statements)

References 34 publications

(30 reference statements)

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“…The Ad-hTERT (or TERT-Adv) has broad targeting antitumor effect, in either hepatoma BEL-7404 or in breast cancer Bcap37 as shown in Figure 6A, B [8]. This is the second paper in literature using the human hTERT promoter to control E1A expression for the study of animal cancer treatment, and is the first paper to show the broad antitumor effect as shown in Figure 6 (A, B).…”

Section: Targeting Dual Gene-virotherapy Of Cancermentioning

confidence: 99%

Targeting gene-virotherapy of cancer

Liu

2006

Cell Res

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Our purpose is to completely elimination of xenograft tumor in animal tumor model in order to work out a protocal for the cure of patient. Gene therapy and viral therapy for cancer have got some therapeutic effects, but both have no great breakthrough. Therefore, we worked out a new strategy called Targeting Gene-Virotherapy of Cancer which is a combination of the advantage of gene therapy and virotherapy. This new strategy has stronger antitumor effect than either of them alone. A tumor specific replicative adenovirus vector ZD55 (E1B 55KD deleted Adv.) which is similar to ONYX-015 in targeting fuction but significant different in construction was produced and various single therapeutic gene was inserted into ZD55. Now such a conception as Targeting Gene-Virotherapy of Cancer was raised and systemically studied before, although there are some works on ONYX-015-tk, -cd or cd/-tk etc. separately. The antitumor effect of ZD55-Gene (for example IL-24 gene) is much better than ZD55 (virotherapy) alone and hundred fold high than that of Ad-IL-24 (gene therapy) alone. ZD55-IL-24 was in preclinal studying in the ZD55-IL-24 therapy, completely elimination of tumor mass was occurred in some mice but not in all mice, that means one gene was not effictive enough to eliminate all the tumor mass in all mice. Therefore two genes with compensative or synergetic effect were inserted into ZD55 sepearately and used in combinction. This strategy was called Targeting Dual Gene-Virotherapy of Cancer (with PCT patent). Then much better results were obtained and all the xenograft tumor masses were completely eliminated in all mice, if two suitable genes were chosen. On the basis of the initiation of two gene results, it was thought about that using two tumors promoter to control the virus vector will be better for the targeting effect and the safty of the drugs. Then double tumor controlled virus vector harboring two genes for cancer therapy was worked out. Better results have been obtained and another patent has been applied. This antitumor strategy could be used to kill all the tumor cells completely in all mice with minimum damage to normal cells.

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Section: Targeting Dual Gene-virotherapy Of Cancermentioning

confidence: 99%

Targeting gene-virotherapy of cancer

Liu

2006

Cell Res

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“…For example, the use of hTERT (human telomerase reverse transcriptase, which is up-regulated in about 90% of tumors) promoter to control adenovirus E1A results in Ad-hTERT, which could target a broad range of cancers such as hepatoma or breast cancers ( Figure 5) as shown in our previous paper [19,26]; this is in contrast to the PSA promoter which can only target prostate cancer. The Ad-hTERT is nevertheless still a targeting virotherapy reagent.…”

Section: Using Two Targeting Promoters and Two Therapeutic Genesmentioning

confidence: 99%

Targeting Gene-Virotherapy of Cancer and its prosperity

Liu

2006

Cell Res

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“…Various nonreplicating Ad vectors applying the hTERT promoter to regulate anticancer therapeutic genes have been reported. [16][17][18][19][20][21] Several oncolytic Ad vectors in which the hTERT promoter regulates the expression of the E1A [22][23][24][25][26][27][28] or E4 29,30 genes have also been described.…”

Section: Introductionmentioning

confidence: 99%

Oncolytic adenovirus that overproduces ADP and replicates selectively in tumors due to hTERT promoter-regulated E4 gene expression

et al. 2005

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We have constructed a novel oncolytic adenovirus (Ad) vector, named VRX-011, in which the replication of the vector is targeted to cancer cells by the replacement of the wild-type Ad E4 promoter with the human telomerase reverse transcriptase (hTERT) promoter. Genes in the Ad E4 transcription unit are essential for Ad replication; therefore, VRX-011 will grow efficiently only in cells in which the hTERT promoter is active, that is, in a wide range of cancer and immortalized cells but not in most somatic cells. Consistent with these expectations, VRX-011 replicated efficiently in all cancer cell lines examined, while its growth was restricted in various primary and normal cells. VRX-011 overexpresses ADP (also known as E3-11.6K), an Ad protein required for efficient cell lysis and release of virions from cells at late stages of infection. This overexpression enhances cell-to-cell spread and could significantly increase antitumor efficacy. In a xenograft model in nude mice, both intratumoral and intravenous administration of VRX-011 effectively suppressed the growth of subcutaneous Hep3B human liver tumors. Also, intravenous delivery of VRX-011 greatly reduced the number and size of A549 human lung cancer cell nodules in a disseminated lung tumor model in nude mice. Importantly, tail vein administration of different doses of VRX-011 in C57BL/6 mice showed minimal liver toxicity. Considering its broad range of lytic replication in cancer cells, its attenuated phenotype in primary cells, its efficacy in suppressing xenografts, and its low toxicity in mouse liver, VRX-011 is a promising candidate for further evaluation as an anticancer therapeutic.

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A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent

Cited by 58 publications

References 34 publications

Targeting gene-virotherapy of cancer

Targeting gene-virotherapy of cancer

Targeting Gene-Virotherapy of Cancer and its prosperity

Oncolytic adenovirus that overproduces ADP and replicates selectively in tumors due to hTERT promoter-regulated E4 gene expression

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