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Dendritic cell . Immunotherapy following autologous peripheral blood stem cell transplantation for patients with childhood cancer

树突状细胞。

基本信息

批准号：
12670755
负责人：
WATANABE Tsutomu
金额：
$ 2.11万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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).

我们研究了自体外周血干细胞移植后树突状细胞免疫治疗儿童癌症患者的可行性。在2000年，我们能够从解冻的外周血干细胞产物的CD 34 ^+细胞部分中通过与白细胞介素（IL）-3、粒细胞/巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子（TNF）-α培养获得功能性树突状细胞，并从它们的CD 14 ^+细胞部分中通过与IL-4和GM-CSF培养获得功能性树突状细胞。2001年，我们能够从解冻的脐带血细胞单位中获得功能性树突状细胞，尽管获得的细胞数量很少。此外，我们能够通过使用Mini MACS分离试剂盒从用G-CSF动员的单采产物中分离树突状细胞。2002年我们对G-CSF动员过程中循环树突状细胞亚群的动力学进行了研究，发现G-CSF动员过程中lin（-）HLA-DR（+）CD 123（+）细胞数量增加，lin（-）HLA-DR（+）CD 11 c（+）细胞数量减少，提示G-CSF诱导DC 2优势状态。此外，我们发现这种DC 2优势状态可以在体外与IL-2转化。这些研究结果表明，树突状细胞免疫治疗是可能的儿童癌症患者自体外周血干细胞移植后，单采产品的调制可能会改变干细胞移植的结果，包括移植物抗宿主病（GVHD）的治疗。