1998 Fiscal Year Final Research Report Summary
Development of double infection method aiming at gene therapy of hepatocarcinoma.
| Project/Area Number |
09470081
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAITO Izumu University of Tokyo, Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (70158913)
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| Co-Investigator(Kenkyū-buntansha) |
KANEKO Shuich Kanazawa University, school of Medicine Associate Professor, 医学部, 助教授 (60185923)
KANEGAE Yumi University of Tokyo, Institute of Medical Science, Research associate, 医科学研究所, 助手 (80251453)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Cre / adenovirus / gene therapy / vector / cancer-specific promoter |
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| Research Abstract |
(1) A method (double infection method) was developed to obtain about 50-fold enhancement in expression level of specific production of a purpose gene under the control of hepatocarcinoma-specific α-fetoprotein (AFP) promoter using adenovirus system.
(2) A mouse model of disseminated hepatocellular carcinoma was established by generation of disseminated tumors in the liver of nude mice after injecting a human hepatocarcinoma cell line Huh7 into the spleen. Selective and specific expression of a marker gene in these disseminated tumors was observed after injection of the above recombinant viruses.
(3) We constructed recombinant adenoviruses containing therapeutic herpes TK gene instead of the marker gene. In tissue-culture experiments, it was observed that the double-infection method using above virus killed tumor cells 5-fole more efficiently than conventional method directly under the control of AFP promoter.
(4) Although inhibition of tumor growth was sometimes observed using the above vector system in the animal experiments, elimination of tumor could not confirmed as far as Huh7 tumor was used.
(5) This new method seems to be applicable for many cancers other than hepatocellular carcinoma, and such experiments are under way for gastric cancer, thyroid cancer etc. Further improvement of the vector system will possibly enable us to establish the method as a promising specific cancer gene therapy.
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