Targeting gene-virotherapy of cancer

Abstract

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.

Oncolytic adenovirus armed with IL-24 Inhibits the growth of breast cancer in vitro and in vivo

“…Traditional replication-defective adenovirus cannot target tumor cells, which limits its therapeutic value. Replication selective virotherapy holds great promise for the treatment of cancer [7-9] whose appealing features include tumor-selective targeting, viral self-spreading in cancer cells, and no cross-resistance to current treatments. One strategy to achieve tumor specificity is the use of tumor- or tissue-specific promoters, such as MUC1, PSA, or PS2, to drive adenoviral genes that are essential for replication [10,11].…”

A novel capsid-modified oncolytic recombinant adenovirus type 5 for tumor-targeting gene therapy by intravenous route

“…In the current study, we adopted the Gene-Viro-Therapy (CTGVT) approach of cancer targeting, as it has demonstrated much higher anti-tumor effects [42, 43]. Many reports have shown that TRAIL could induce the selective death in a wide range of human cancer cells [44–46].…”

“…Therefore, researchers have used TRAIL as a foreign gene for cancer treatment in CTGVT research [47–49]. Although all of those treatments were effective when tested in vivo in nude mouse xenografts by IT injection [42, 43, 50], these studies did not carry out the animal experiments with IV injection of the vector, and such data are necessary for clinical evaluation. Furthermore, CTGVT research tended to show effective treatment of hepatic carcinoma but without discussing the problem of liver enrichment if the vector needs to be used to target other tissues [33].…”

MicroRNA-145 regulates oncolytic herpes simplex virus-1 for selective killing of human non-small cell lung cancer cells

“…Recently, the use of oncolytic viruses has been identified as a novel potential strategy for cancer treatment owing to its capacity to destroy tumor cells both in vitro and in vivo with minimal collateral damage to normal cells [6]. In recent decades, a number of oncolytic virus vectors have been developed with mutations in genes associated with virulence or viral DNA synthesis to confine viral replication to cancer cells and avoid causing disease [7,8]. One approach to engineering replication selectivity is the deletion of viral genes, which causes inefficient viral replication in normal cells but expansion in tumor cells.…”