Project/Area Number |
12670755
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | The University of Tokushima |
Principal Investigator |
WATANABE Tsutomu University of Tokushima, School of Medicine, Instructor, 医学部, 助手 (70314862)
|
Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro University of Tokushima, School of Medicine, Professor, 医学部, 教授 (20035471)
河野 嘉文 徳島大学, 医学部・附属病院, 講師 (20260680)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | childhood cancer / Autologous peripheral blood stem cell transplantation / Dendritic cell / Immunotherapy / 造血幹細胞移植 / 末梢血幹細胞移植 / 小児がん |
Research Abstract |
We investigated the feasibility of dendritic cell immunotherapy following autologous peripheral blood stem cell transplantation for patients with childhood cancer. In 2000, we were able to obtain functional dendritic cells from the CD34^+ cell fraction of the thawed peripheral blood stem cell products by culturing with interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α, and from the CD14^+ cell fraction of them by culturing with IL-4 and GM-CSF. In 2001, we were able to obtain functional dendritic cells from the thawed cord blood cell units, although the number of obtained cells was small. Furthermore, we were able to isolate dendritic cells from the apheresed products, which were mobilized with G-CSF, by using the Mini MACS isolation kit. In 2002, we also studied the kinetics of the circulating dendritic cell subset during G-CSF mobilization, and we found that the number of lin(-)HLA-DR(+)CD123(+) cells increased while the number of lin(-)HLA-Dr(+)CD11c(+) decreased during G-CSF mobilization, which suggested that G-CSF induced the DC2 dominant state. Further, we found that this DC2 dominant state can be conversed with IL-2 in vitro. These findings suggest that dendritic cell immunotherapy is possible for patients with childhood cancer following autologous peripheral blood stem cell transplantation, and the modulation of the apheresed products may change the outcome of stem cell transplantation including treatment of graft versus host disease (GVHD).
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