| Project/Area Number |
11670986
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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 |
Hematology
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TAKAHASHI Masuhiro Faculty OF Medicine, Niigata University, Professor, 医学部, 教授 (90179531)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Tatsuo Medical Hospital, Niigata University, Associate Professor, 医学部・附属病院, 助教授 (00272849)
NARITA Miwako Faculty OF Medicine, Niigata University, Assistant, 医学部, 助手 (30281009)
小池 正 新潟大学, 医学部・附属病院, 助教授 (30170161)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | dendritic precursor cells / myelodendritic leukemia / leukemia derived dendritic cells / CTL line / anti-leukemic immunotherapy / myelodendric leukemia / dendritic cells / mupelodendritic leukemia / anti-leukemic immune-Therapy / 樹状細胞 / 急性白血病 / 白血病性樹状細胞 / CDla / CD83 / 混合白血球培養 / 抗原呈示能 |
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| Research Abstract |
Objective : In order to elucidate the mechanism of immunological escape of leukemia cells and establish an effective anti-leukemia immunotherapy, we tried to generate dendritic cells from leukemia cells in patients with acute myelogenous leukemia (AML). Using these leukemia derived dendritic cells, we investigated leukemia cell-associated T cell anergy. Materials and Methods : Leukemia cells of 30 patients with AML were cultured with GM-CSF, IL-4, and TNF-α. Cultured leukemia cells were evaluated for antigen presenting ability by mixed leukocyte culture. Normal lymphocytes, which were co-cultured with leukemia blasts in 1st MLC, were cultured with leukemia derived dendritic cells in 2nd MLC. Results : In culture of leukemia cells from 21 out of 30 patients examined, cells with stellate morphology were observed and cell fraction with Cdla^+ and/or CD83^+ were demonstrated to be present in the culture. Autologous MLC using lymphocytes obtained in remission phase as responders as well as allogeneic MLC demonstrated the antigen presenting ability in leukemia derived dendritic cells. Leukemia cells of FAB-M0, M1, M2, M3 or M6 morphology/phenotype gave rise to dendritic cells as well as leukemia cells of M5. Leukemic origin of dendritic cells were suggested by in situ hybridization. By being co-cultured with CD80-negative leukemia blasts, the response of normal lymphocytes to leukemia derived dendritic cells cultured from the same individual as that of leukemia blasts was markedly reduced, compared with the lymphocytes cultured with leukemia blasts from the different individual as leukemia blasts. Conclusion : Escape of leukemia cells from anti-leukemia immunity was suggested to be associated with T cell anergy caused by leukemia blasts. In addition, the present study implied that leukemia derived dendritic cells could be applied efficiently in anti-leukemia immunotherapy.
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