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

2004年：(1)我们改进了从肿瘤细胞中提取的mRNA转导DC的方法。与单独使用电穿孔相比，使用脂质体和电穿孔可显著提高基因转导效率。接下来，我们评价了转导MC38/CEA肿瘤细胞基因(MRNADC)的DC疫苗对小鼠肺转移模型的保护作用。结果表明，与肿瘤裂解物致敏的DC和多肽致敏的DC相比，mRNADC刺激的T细胞产生的干扰素-r和细胞毒活性显著增加。与裂解物DC和多肽DC相比，mRNADC免疫小鼠的肺转移数明显减少。(2)研究IL-12和IL-18基因转导的树突状细胞肿瘤融合疫苗的抗肿瘤作用。结果表明，IL-12和IL-18基因的转导对神经母细胞瘤肝转移具有极强的保护和治疗作用。2005：(1)从MKN45肿瘤细胞中提取的mRNA转导人单核细胞来源的DC(MKN45mRNADC)。经MKN45mRNADC刺激后的T淋巴细胞产生明显的干扰素-γ，对MKN45肿瘤细胞具有明显的杀伤活性。(2)研究DC-肿瘤融合疫苗在晚期或复发期胃肠癌患者中的I期试验。这项研究得到了我校伦理委员会的批准。在获得知情同意后，13名患者参加了这项研究。无不良反应，临床反应1例部分缓解，5例病情稳定，7例病情恶化。

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.