| In recent ten years tumor gene therapy has achieved significant progress, whereas the relative clinical research is still in quite another situation. The main reason is that the traditional scheme of gene therapy introduce the methods of non-replicative virus or physical chemistry. Low gene transfer rate and expression capacity, along with the characteristic of non-target to tumor cells, are the reasons that we haven't yet healed the malignant tumor by these methods. Lately a new kind of oncolytic replicative virus has gained the attractions from allover the world for its surprising effect on tumor therapy. Because of some discrepancies between the tumor cells and the normal ones, the virus can specially proliferate in the tumor cells, but not in the normal cells, so that it can specially kill the tumor cells. Among these viruses, the most effective one is the Elb-55Kda deficiented replicative virus(ONYX-015) developed by the American ONYX Pharmacy Company. The curative effect is still not very ideal when ONYX-015 administered singly and the fulfill of its therapeutic effect must be in virtue of the chemical drugs. Therefore we imagine such a method that is to insert an anti-cancer gene into the genome of the virus, so the anti-cancer gene can be specially and highly expressed in the tumor cells by the viruses' characteristically proliferating in the tumor cells. The new scheme which can exploit the virtues of virus therapy and gene therapy is named as gene-virus therapeutics. It overcomes the disadvantages of7anticancer agent because the virus cannot replicate efficiently. The tumor specific adenovirus can get a satisfied effect with targeted gene therapy theoreticaly; however, due to its fatal side effect in high dose, it is necessary to reach for better control of replication and gene expression.In summary, the tumor-specific replication-competent adenovirus can specially replicate in tumor cells and the transduced gene in the tumor cells can copy and multiply to millions of times by the viruses' characteristically proliferation in tumor cells. The new method overcomes disadvantages as low transfer rate, low expression and non-target of traditional tumor gene therapy. IL- 12 is an effective inducer of anticancer immune responses and the resulted anticancer responses are effective in colon carcinoma, but high dosage may cause severe side effect. So precise control of gene expression as well as tumor selective replication should be studied next. Based on these results, we conclude that the new gene-virus therapeutics leads to more effective anticancer therapies and may aid in the future conquer of colon cancer.11traditional gene therapy, such as low transfer rate, low expression capacity and non-target tropism.Interleukin- 12 (IL- 12) is a disulfide-linked heterodimer molecule produced predominantly by professional antigen presenting cells. It promotes the induction of sundry biological effects with significant relevance to anticancer immunity, such as enhancing a T(H)1 helper response, an in vivo antiangiogenic effect, induction of adhesion molecules that assist in lymphocyte homing to sites of tumor growth. Also Interleukin- 12 (IL- 12) can directly induce and enhance the activity of natural killer (NK) cells, lymphokine activated killer (LAK) cells and cytotoxic T lymphocytes (Cm). IL-l2 also stimulates IFN-gamma production from both T cells and NK cells.Now we have established a kind of tumor-specific replication-competent adenovirus vector system that carry Interleukin- 12 gene and the preliminary study of its anti-cancer effect has been carried out.1. Constructions of Tumor-specific replication-competent adenovirus-mediated transfer of Interleukin-12 gene.The vector pXC1 was digested at the site of 3329bp by the endonuclease BgLII, then was partially digested by the endonuclease HindIII. What has been obtained is a new vector backbone in which the fragment from 2809 bp to 3329 bp is deficient compared with PXC1. A pair of DNA oligonucleotide fragments were joined with the...
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