| Project/Area Number |
12670979
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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 |
FURUKAWA Tastuo Niigata University, Medical Hospital, Associated professor, 医学部・附属病院, 助教授 (00272849)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Tadashi Nagaoka Red Cress Hospital, Doctor, 内科医長
TAKAHASHI Masuhiro Faculty of Medicine, Niigata University, Professor, 医学部, 教授 (90179531)
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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 |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | leukemia / dendritic cell / hematopoietic stem cell transplantation / GVHD / CTL / mixed chimerism / TCR / 同種骨髄移植 |
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| Research Abstract |
1. The specificity of GVL for the leukemia cell in the allo-HSCT remains to be investigated. We used dendritic cells and leukemia specific fusion pepetides to establish CTL line for leukemia cells. We demonstrated the oligo-clonality of CTL line CD4 T cells for leukemia specific fusion peptide using the spectratyping of TCR CDR3 region. We also demonstrated cytotoxicity of donor CTL line cells to recipient CML cells with a peptide specific manner. These findings suggested that donor T cell populations might be able to mediate recipient leukemia cell specific GVL effect after allo-HSCT.
2. Even when the leukemia specific abnormal peptide such as bcr/abl fusion peptide was undetermined, we examined the method to make leukemia cells express co-stimulatory molecules and enhance presentation of leukemia-specific antigens. The method culturing leukemia cells with GM-CSF, IL-4 and TNFα in patients with AML patients, induced leukemia-derived antigen presenting dendritic cells with costimulatory molecules. This method can be applied efficiently in anti-leukemia immunothrapy.
3. We also demonstrated the contribution of donor- or recipient-derived TNF α-308 and donor-derived IL-10-G gene polymorphism to the development of sever aGVHD and cGVHD following allo-HSCT respectively. The difference in the cytokine gene polymorphism may reflect differences in the pathogenesis and the clinical features of each GVHD type.
4. We then, analyzed the chimerism after allo-HSCT and demonstrated that some patients revealed mixed chimerism without relapse, and that complete donor chimerism was achieved within 6 months after HSCT in such cases. This analysis suggested that reconstituting immune system after 6 months might play an important role in the eradication of malignant cells after HSCT.
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