| Project/Area Number |
08457272
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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 |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TANI Kanezaburo Univ.of Tokyo, Inst.of Med.Sci., Associate Professor, 医科学研究所, 助教授 (00183864)
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| Co-Investigator(Kenkyū-buntansha) |
ASANO Shigetaka Univ.of Tokyo, Inst.of Med.Sci., Professor, 医科学研究所, 教授 (50134614)
TANIGUCHI Yoshikuni Central Animal Laboratory, Section Head, 室長 (10072406)
TAKAHASHI Satoshi Univ.of Tokyo, Inst.of Med.Sci., Clinical Associate, 医科学研究所, 助手 (60226834)
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| Project Period (FY) |
1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1996: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | common marmoset / peripheral blood stem cells / gene therapy / multidrug resistant gene / GM-CSF gene / B7-1 gene / IL-12 gene / retroviral vector |
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| Research Abstract |
We have established common marmoset model system where we can transduce multi-drug resistant gene (MDR1) into peripheral blood stem cells (PBSC) efficiently using retroviral vectors in vitro. We transplanted the MDR1-gene transduced PBSC to lethally irradiated common marmoset and the clinical course was observed. On day 220 after the transplantation, we detected MDR1 gene in the peripheral neutrophils and lympho-cytes using PCR method. Our results demonstrated the possibility of transducing target gene with the selection marker of MDR1 gene into long-term reconstituting hematopoietic stem cells. Based on this result, we are seeking the possibility of transducing bcr/abl or pml/rar gene using retroviral vector into marmoset PBSC and are going to establish human leukemia in common marmoset. Our current technical problem is the instability of retroviral producer cells because of the toxicity of the bcr/abl or pml/rar gene product. To solve this problem, we are establishing transient retro
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viral producer cell line using phi NX producer. By the use of this transient system, we will be able to obtain high titer retroviral vectors carrying bcr/abl or pml/rar. On the otherhand, we have also been studying the murine autologous leukemia/lymphoma model system to develop the gene therapy for leukemia/lymphoma. Autologous malignant cells of leukemia/lymphoma transduced with GM-CSF and/or B7-1 gene induced the protective immunity to host mice against the challenge of the type counterpart cells. Particularly, the combined effects of the two genes were demonstrated in vivo. Also we studied the effectiveness of IL-12 gene transduced autologous murine lung cancer cells against the challenge of the wild type counterpart lung cancer cells. Interestingly, therapeutic effects of the autologous lung cancer cells were also demonstrated. Our current results suggested strongly the possible antitumor effects of gene transduced malignant cells in vivo. The establishment of our marmoset human leukemia model would be helpful for eveluating the safety and effectiveness of newly developed vector system for gene therapy, in future. Less
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