权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Clinical application of NKT cell immune system for lung cancer

NKT细胞免疫系统在肺癌治疗中的临床应用

基本信息

批准号：
15209045
负责人：
FUJISAWA Takehiko
金额：
$ 32.12万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15209045/
关键词：
NKT cell dendritic cell clinical trial

项目摘要

We performed αGalactosylceramide-pulsed Dendritic cells in patients with lung cancer. Patients with advanced non-small cell lung cancer or recurrent lung cancer received intravenous injections of αGalCer-pulsed DCs (1x10^9/m^2) to test the safety, feasibility, and clinical response. Immunomonitoring was also performed in all completed cases. Eligible patients underwent peripheral blood leukapheresis, and peripheral blood mononuclear cells (PBMCs) were collected and further separated by density gradient centrifugation. PBMCs were cultured with human granulocyte-macrophage colony-stimulate factor (GM-CSF) for 1-2 weeks and pulsed with specific ligand, α-Galactosylceramide on the day before administration.Seventeen patients were enrolled in this study. The frequency of peripheral blood NKT cells in all patients was measured by FACS analysis and IFN-γ production after restimulation with αGalCer in PBMCs was measured by ELISPOT assay. Patients with marked increase of FN-γ production following the administration of αGalCer-pulsed DC showed relatively long survival and time to tumor progression, while poor responder of IFN-γ production showed very poor prognosis. This is the first report to show the crucial role of IFN-γ at NKT cell immunotherapy. With these results, the role and mechanisms of IFN-γ production and anti-tumor immune response will be discussed.

我们在肺癌患者中进行了α半乳糖神经酰胺脉冲的树突状细胞。晚期非小细胞肺癌或复发性肺癌患者接受静脉注射α GalCer脉冲的DC（1 × 10^9/m^2），以测试安全性，可行性和临床反应。在所有完成的病例中也进行了免疫监测。符合条件的患者接受外周血白细胞去除术，收集外周血单个核细胞（PBMC），并通过密度梯度离心进一步分离。用人粒细胞-巨噬细胞集落刺激因子（GM-CSF）培养PBMCs 1-2周，并于给药前1天用特异性配体α-半乳糖神经酰胺（α-Galactosylceramide）冲击。所有患者的外周血NKT细胞频率通过FACS分析测量，αGalCer再刺激PBMC后IFN-γ产生通过ELISPOT测定。α GalCer脉冲的DC给药后FN-γ产生显著增加的患者显示相对较长的生存期和肿瘤进展时间，而IFN-γ产生的不良反应者显示非常差的预后。这是第一份显示IFN-γ在NKT细胞免疫治疗中的关键作用的报告。结合这些结果，对IFN-γ产生和抗肿瘤免疫应答的作用和机制进行了讨论。