1996 Fiscal Year Final Research Report Summary
Fundamental studies on combination gene therapy for human cancer
| Project/Area Number |
07457255
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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 |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
AKIYOSHI Tsuyoshi MEDICAL INSTITUTE OF BIOREGULATION,JYUSHU UNIVERSITY,PROFESSOR, 生体防御医学研究所, 教授 (70038660)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Kinya MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,LECTURER, 生体防御医学研究所, 助手 (30271117)
HARAGUCHI Masaru MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,ASSISTANT PROFESSOR, 生体防御医学研究所, 講師 (40228531)
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| Project Period (FY) |
1995 – 1996
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| Keywords | gene therapy / cytokine gene / costimulatory molecule / MAGE gene / vector / combination therapy / human cancer |
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| Research Abstract |
To investigate the possibility of immunological combination gene therapy for human cancer, we transfected tumor cells derived from human gastrointestinal carcinoma with various cDNAs, including IL-2, IL-6, CD80, CD86 or MAGE-3, using retrovirus or adenovirus vector. The cells transfected with these genes were characterized and the immunogenicity of these cells was then evaluated. Gastric carcinoma cells transfected with IL-2 cDNA using retrovirus vector induced specific cytoxic T lymphocytes (CTL) after in vitro stimulation of especially autologous peripheral blood mononuclear cells (PBMC) with these cells. SCID-PBL/hu mice which had been constructed with human PBMC and thereafter had been given human tumor cells i.p. were treated in vivo with recombinant adenovirus vector expressing IL-6 cDNA.The induction of specific CTL against allogenic and autologous tumor cells was observed from human precursor T cells, and the prolongation in the survival of these mice or the inhibition of growth and metastasis in human cancers was also demonstrated. Although the transfection of CD80 or CD86 cDNA into human cancer cells was unsuccessful, MAGE-3 gene transfected gastric carcinoma cells produced MAGE-3 protein and were lysed by MAGE-3 specific CTL in vitro. These findings suggested that human carcinoma cells transfected with these genes may be useful tool for the strategy of immunological combination gene therapy for human cancer.
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