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Development of new anti-cancer therapy and anti-liver cirrhosis treatment using by NKT cells activated withα-Galcer.

利用α-Galcer激活的NKT细胞开发新的抗癌疗法和抗肝硬化疗法。

基本信息

批准号：
19689027
负责人：
YANAGISAWA Kazuhiko
金额：
$ 17.22万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (A)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19689027/
关键词：
NKT細胞腫瘍免疫肝硬変癌転移抑制

项目摘要

We reported hypo responsiveness of NKT cells in cancer-bearing state. In animal models, CD11b+ Gr1+ cells are increased in cancer-bearing state, which produce nitric oxide and suppress NKT cell functions. We reported also all trans retinoic acid (ATRA) can absolve hypo responsiveness of NKT cells in cancer-bearing state. We showed clearly in this study that CD11b+ Gr1+ cells in animal models were CD33+ CD14- CD11b+ cells in human, and this population suppressed NKT cell functions in cancer patients. We also indicated that ATRA is able to absolve hypo responsiveness of NKT cells in cancer patients in vitro. CD11b+ Gr1+ cells which increased in cancer patients more expressed VEGF than in healthy donors, but FOXP3 expressions were no significant difference between cancer patient and healthy donors. There was a trend toward that CD33+ CD14- CD11b+ cells were reduced after cancer therapy using with anti VEGF antibody. Based on the result of this study, we indicate that anti VEGF antibody which is already used as cancer therapy drug could be have ability of reducing immune suppression in cancer patient. We believe that this result will be important basic study for new cancer therapy using with NKT cells and we can use this treatment for several cancer therapy commencing with colorectal cancer.

我们报告了 NKT 细胞在癌症携带状态下的低反应性。在动物模型中，CD11b+ Gr1+ 细胞在癌症状态下增加，产生一氧化氮并抑制 NKT 细胞功能。我们还报道了全反式视黄酸（ATRA）可以消除处于癌症状态的 NKT 细胞的低反应性。我们在这项研究中清楚地表明，动物模型中的 CD11b+ Gr1+ 细胞是人类中的 CD33+ CD14- CD11b+ 细胞，并且该群体抑制癌症患者中的 NKT 细胞功能。我们还表明，ATRA 能够在体外消除癌症患者 NKT 细胞的低反应性。癌症患者中增加的CD11b+ Gr1+细胞比健康供者更表达VEGF，但癌症患者和健康供者之间FOXP3表达无显着差异。使用抗 VEGF 抗体进行癌症治疗后，CD33+ CD14- CD11b+ 细胞有减少的趋势。基于这项研究的结果，我们表明已经用作癌症治疗药物的抗VEGF抗体可能具有减少癌症患者免疫抑制的能力。我们相信，这一结果将成为使用 NKT 细胞进行新癌症治疗的重要基础研究，我们可以将此治疗用于从结直肠癌开始的多种癌症治疗。