Adjuvant immuno-gene therapy for surgical treatment using dendritic cells

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The outcome of the cancer treatment would be greatly improved if immuno-gene therapy could serve as an adjuvant therapy for surgical operation. We hypothesized that the therapy using dendritic cells (DCs) could be one of the measures for achieving this goal. In this grant period, we have shown that the feasibility of gene modification of DCs using retroviral and adenoviral vectors. Especially with adenoviral vectors, we could transduce genes into more than 60% of the monocyte derived human DCs. Using these vectors, we have also shown in the mouse models that the immune response in vitro and in vivo could be regulated using DCs genetically modified to express cytokines including IL-10, viral IL-10, IL-12 and other molecules. Furthermore, we have shown that the maturation, proliferation and mobilization of the dendritic cells in the host could be modulated by the systemic circulation of Flt3-L expressed with in vivo electroporation of Flt3-L gene. These results strongly suggest that DCs strongly affect the immune response and gene therapy could be one of the effective ways to modulate immune responses especially in vivo. This strategy could applied for cancer therapy in the next few years.