Tumor vaccine therapy by dendritic cells transducd with mRNA of tumor cells

通过转导肿瘤细胞 mRNA 的树突状细胞进行肿瘤疫苗治疗

基本信息

批准号：
16591272
负责人：
IINUMA Hisae
金额：
$ 2.05万
依托单位：
Teikyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591272/
关键词：
dendritic cell tumor vaccine oncogene mRNA 遺伝子導入ワクチン

项目摘要

2004: (1) We modified the method of transduction of mRNA extracted from tumor cells into DC. By using the liposome and electroporation, efficiency of gene transduction was increased significantly as compared with that of electroporation only. Next, we assessed the protective effect of the DC vaccine transduced with MC38/CEA tumor cell mRNA (mRNA DC) in mouse lung metastasis model. We demonstrated that the IFN-r production and cytotoxic activity of T cells stimulated with mRNA DC increased significantly compared with those of DC pulsed with tumor lysate (lysate DC) or DC pulsed with peptide (peptide DC). The number of lung metastasis in mice vaccinated with mRNA DC decreased significantly compared with that of mice vaccinated with lysate DC or peptide DC. (2) We studied the anti-tumor effects of IL-12 and IL-18 gene-transduced DC tumor fusion vaccine. It was shown that the transduction of IL-12 and IL-18 genes can induce extremely strong protective and therapeutic effects on liver metastasis of neuroblastoma.2005: (1) Human monocyte-derived DCs were transduced with mRNA extracted from MKN45 tumor cells (MKN45mRNA DC). T lymphocytes stimulated with MKN45mRNA DC showed the significant level of IFN-γ and cytotoxic activity to MKN45 tumor cells. (2) We studies phase I trial of DC-tumor fusion vaccine in gastrointestinal cancer patients with advanced or recurrent stage. This study was approved in the ethics committee of our university. Thirteen patients were enrolled in this study after informed consent was obtained. There were no adverse effects and clinical response was partial response in one patient, stable disease in five patients and disease progression in seven patients.

2004年：（1）我们修改了从肿瘤细胞中提取到DC的mRNA转移方法。通过使用脂质体和电穿孔，与仅电穿孔相比，基因转移的效率显着提高。接下来，我们评估了小鼠肺转移模型中用MC38/CEA肿瘤细胞mRNA（mRNA DC）转移的直流疫苗的受保护作用。我们证明，与肿瘤裂解物（裂解物DC）或用肽（肽DC）的DC脉冲相比，用mRNA DC刺激的T细胞的IFN-R产生和细胞毒性显着增加。与用裂解物DC或胡椒直流接种的小鼠相比，接种mRNA DC接种的小鼠中的肺转移数量显着减少。（2）我们研究了IL-12和IL-12基因转导DC肿瘤融合疫苗的抗肿瘤作用。结果表明，IL-12和IL-18基因的转导可以诱导对神经母细胞瘤的肝转移的极强保护和治疗作用。2005：（1）用从MKN45肿瘤细胞中提取的mRNA（MKN45MRNA DC）将人单核细胞衍生的DC转移。用MKN45 mRNA DC刺激的T淋巴细胞显示出对MKN45肿瘤细胞的IFN-γ和细胞毒性活性的显着水平。（2）我们研究了晚期或经常性阶段的胃肠道癌患者中DC肿瘤融合疫苗的I期试验。这项研究已在我们大学的伦理委员会批准。获得知情同意后，已入学13名患者。没有不良反应，临床反应是一名患者的部分反应，五名患者的稳定疾病和七名患者的疾病进展。