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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：（1）我们改进了从肿瘤细胞中提取的mRNA转导DC的方法。通过脂质体介导和电穿孔，基因转导效率比单纯电穿孔有显著提高。接下来，我们评估了用MC 38/CEA肿瘤细胞mRNA（mRNA DC）转导的DC疫苗在小鼠肺转移模型中的保护作用。我们证明，IFN-γ的生产和细胞毒活性的T细胞刺激mRNA DC相比，那些与肿瘤裂解物（裂解物DC）或DC脉冲与肽（肽DC）的DC脉冲显着增加。与裂解DC或肽DC免疫小鼠相比，mRNA DC免疫小鼠的肺转移数目显著减少。(2)我们研究了IL-12和IL-18基因转导的DC肿瘤融合疫苗的抗肿瘤作用。研究表明，IL-12和IL-18基因的转导对神经母细胞瘤的肝转移具有极强的保护和治疗作用。2005：（1）用从MKN 45肿瘤细胞提取的mRNA转导人单核细胞来源的DC（MKN 45 mRNA DC）。经MKN 45 mRNA DC刺激的T淋巴细胞对MKN 45肿瘤细胞具有明显的IFN-γ和细胞毒活性。(2)我们研究了DC-肿瘤融合疫苗在晚期或复发期胃肠道癌患者中的I期试验。本研究已获得我校伦理委员会的批准。在获得知情同意后，13例患者入组本研究。无不良反应，1例患者的临床反应为部分反应，5例患者病情稳定，7例患者病情进展。