| Project/Area Number |
12671198
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
GUNJI Yoshio Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (60241957)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMADA Hideaki Chiba University, Graduate School of Medicine, Lecturer, 医学部・附属病院, 助手 (20292691)
MATSUBARA Hisahiro Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (20282486)
OCHIAI Takenori Chiba University, Graduate School of Medicine, PROFESSOR, 大学院・医学研究院, 教授 (80114255)
TAGAWA Masatoshl DEPARTMENT OF PATHOLOGY, CHIBA CANCER CENTER, CHIEF, 病理研究部, 部長 (20171572)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | DENDRITIC CELLS / ADENORICUS VECTOR / TH1 TYPE CYTOKINES / COLON 26 / アデノウイルスベクター / Colon 26 / Th1サイトカイン / IL-2 |
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| Research Abstract |
We have demonstrated that retrovirally transduced Th-1 type cytokine genes (Interleukin 2, 12, 15, 18 ) not Th-2 type cytokine genes( IL-4, IL-6) into colon.26 tumor cells elicit anti-tumor-effect. Growth of colon 26 /Th-1 type cytokine genes were successfully suppressed in syngeneic mice in our laboratory. In that experimental system, combined s.c. injection of colon 26/GM-CSF and /IL-4 tumor cells also elicit anti-tumor effect using potential activity of dendritic cells (DC)., Stimulation of the anti-tumor immune response by DC is critical to initiate anti-tumor immune machinery. To enhance this effect in tumor-bearing mice, bone marrow (BM) derived DC cells from Ba1b/C mice were genetically engineered to produce IL-2 by ex-vivo infection with a recombinant defective adenovirus (AxCAhIL-2). DC cells were generated from bone marrow cells cultured with mouse IL-4 (1000 u/ml) and GM-CSF(1000 u/ml) for 5 through 7 days and infected with AxCAhIL-2 with MOI 30. Those adenovirally transduced IL-2 gene produced high amount of IL-2 protein from DCs after infection. Intratumoral injection of IL-2 expressing DCs suppressed tumor growth profoundly, and prolonged the survival of the mice treated with those DCs (p<0.001). Multiple injection of DCs/AxCAhIL-2 enhanced the anti-tumor effect and increased the infiltration of macrophage to the peripheral site of tumor. These data suggest the possibility of DC/adenovirus mediated cytokine gene therapy.
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