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Studies on the Preparation、Anticancer Effect and Safety of Double-Tareting Replicative Adenovirus with Plaminogen Kringle 5 and IL-24 in Vitro

Author: ZhangJinHe
Tutor: DaiPing；LiuXinYuan
School: East China Normal University
Course: Biochemistry and Molecular Biology
Keywords: Tumor-specific adenovirus Telomerase reverse transcriptase promoter E1A gene E1B 55kDa gene Gene -viral treatment K5 mda-7/IL-24
CLC: R73-3
Type: Master's thesis
Year: 2006
Downloads: 104
Quote: 0
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Abstract


Tumor-specific adenovirus is a class of promising anticancer drugs, these viruses can specifically replicate in tumor cells, proliferation, thus killing the tumor cells and normal cytotoxic smaller. Construction of tumor-specific adenovirus, there are two main ways: First, the use of tumor-specific promoters to control viral replication essential gene, such as the control of the adenovirus E1A gene. The laboratory using the hTERT promoter to replace the wild-type adenovirus E1A gene promoter, build a new proliferation of tumor-specific adenovirus Ad. TERT. Another method is to delete the virus is essential for replication in normal cells, while replication in tumor cells unwanted gene. The Laboratory of the adenovirus E1B 55kDa protein knockout construct another class of tumor-specific proliferation of adenovirus ZD55-Gene. These two constructs the tumor-specific adenovirus have demonstrated excellent tumor inhibitory effect. To further enhance the anti-cancer effect of tumor-specific proliferation of the virus, the laboratory has proposed a new cancer treatment strategy: anti-cancer gene in the tumor-specific proliferation of viruses, cancer gene therapy and viral therapy combined, said as tumor gene-viral treatment. The tumor gene viral treatment retains the ability of the virus to kill cancer cells, the same time as virus replication in tumor cells, but also greatly increase the expression amount of the anticancer gene in tumor cells. This has a great significance for achieving a safer and more effective cancer treatment, the work of building became targeting hTERT-positive and p53 protein loss of function of the tumor-specific adenovirus TD55 upcoming adenovirus E1A gene promoter with hTERT promoter in place of the deleted E1B 55kDa protein gene. Tumor angiogenesis play a very important role in the process of tumor development, such as the key steps of tumor growth, metastasis are dependent tumor angiogenesis to provide nutrition. This work will inhibit angiogenesis of human plasminogen the original K5 and insert mda-7/IL-24 on the TD55, TD55-K5 building became a recombinant adenovirus the TD55-IL-24 and TD55-IL-24-K5. Insert the K5 inhibit tumor angiogenesis, and IL-24 is able to inhibit angiogenesis while also specific manner to promote apoptosis of tumor cells, coupled with targeted oncolytic adenovirus oncolytic effect from theory, TD55-gene system targeted gene - viral treatment effect will be better than a simple gene therapy will be better than a simple virus treatment, provide an ideal platform for tumor targeting gene - viral treatment. Cell experiments preliminary evidence of the activity of the recombinant adenovirus has high security and high kill tumor cells, such as the TD55 than in normal cells HMCS Onyx015 1.5 times better, recombinant adenovirus TD55-IL-24 to kill tumor cells a Bcap37 capacity than Onyx015 of intensity close to 100 times.

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