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免疫担当細胞の自然がん監視能を活用した新規ドラッグデリバリーシステムの開発

开发利用免疫活性细胞天然癌症监测能力的新型药物递送系统

基本信息

批准号：
20015025
负责人：
田畑泰彦
金额：
$ 5.25万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

本研究の目的は、「遺伝子治療法」と「免疫・細胞療法」とを融合した新しいがん治療DDS技術を創製し、その治療効果について検証することである。すなわち、がんへ直接働くあるいは他の細胞に働いて免疫・細胞療法活性を高める作用をもつタンパク質をコードしたプラスミドDNAを免疫担当細胞へ導入することによって、免疫担当細胞を遺伝子改変する。次に、その遺伝子改変免疫担当細胞をがん治療に用いる。このことにより、上述した「遺伝子治療法」および「免疫・細胞療法」で問題となっていた、プラスミドDNAの体内動態制御および免疫担当細胞の活性増強の両方を解消することが可能であり、がん治療の効果増強が期待される。本年度は、前年度の結果をもとに細胞をマクロファージから樹状細胞(DC)に変えて、細胞への導入プラスミドDNAとしては抗がんサイトカインであるインターロイキン(IL)12をコードするプラスミドDNAを用いた。異なる多糖と異なるカチオン化試薬を用いて様々なカチオン化多糖を作製し、DCへのプラスミドDNA導入作用について調べた結果、スペルミン導入デキストランが優れていることがわかった。そこで、このベクターを用いてIL12プラスミドDNAをDCへ導入した。プラスミド導入DCは2週間にわたってIL12タンパク質を分泌した。得られたIL12プラスミドDNA導入DCを担がんマウスの尾静脈より投与した。その結果、DCのみの投与に比較して、高い抗がん活性が認められた。プラスミド導入DCを投与したマウス肝臓よりリンパ球を採取して、リンパ球とがん細胞とを混合して培養したところ、がん細胞が死滅した。この結果は、DCにより体内のがん免疫応答が高まったことを示している。

In this study, the purpose of this study is to improve the effectiveness of the treatment of DDS by the combination of the method of treatment of children and the method of immune cell therapy. The immunological activity of the method of immunocytochemistry was higher than that of the control group. The immune response of the immune system was changed from the cell to the cell, and the immune response was changed from the cell to the cell. The children of the second and second generations were changed to be immunized to act as cellular agents in the treatment of diseases. To improve the activity of immune system in vivo, to improve the activity of immune system in vivo, to improve the ability of immune response, to improve the effect of treatment and treatment, it is necessary to strengthen the activity of immune system in vivo, and to strengthen the activity of immune system in vivo. The results of this year and the previous year show that there is no significant difference between this year and the previous year. In this year and the previous year, the results of this year and the previous year show that the number of cells in the current year and the previous year is different. This year and the previous year, the results of this year and the previous year show that in the current year and the previous year, in the current year and the previous year, the results of this year and the previous year show that the number of cells in the current year and the previous year is similar to that of the previous year. This year and the previous year, the results of this year and the previous year show that in the current year and the previous year, the results of this year and the previous year have shown that the cells are not in the shape of a cell (DC). In this year and the previous year, the results of this year and the previous year show that there are The polysaccharides were used to treat polysaccharides. The polysaccharides were used to make polysaccharides, DC polysaccharides were added to the polysaccharides, and DNA was added to the polysaccharides. Please use the IL12 DC to enter the DNA. During the period of DC 2, you need to enter the IL12 to secrete a lot of chemicals. You have to pay attention to IL12 and DNA into the DC. The results were compared with those of DC, and the high anti-tumor activity was confirmed to be sensitive. Throw the ball into the DC and make sure that the cell is mixed and the cell is dead. The results showed that the immune response in the body of DC mice was significantly higher than that of normal controls.