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

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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.