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Adjuvant immuno-gene therapy for surgical treatment using dendritic cells

使用树突状细胞进行手术治疗的辅助免疫基因疗法

基本信息

批准号：
12470237
负责人：
TAHARA Hideaki
金额：
$ 8.96万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470237/
关键词：
tumor immunology dendritic cells gene therapy cytokine NK cells IL-18 adenoviral vector retroviral vector インターロイキン in vivo electroporation アデノウイル・スベクターレトロウイルス・ベクター

项目摘要

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.

如果免疫基因治疗能作为外科手术的辅助治疗，将会大大改善癌症的治疗结果。我们假设，使用树突状细胞(DC)的治疗可能是实现这一目标的措施之一。在这一资助期间，我们已经证明了利用逆转录病毒和腺病毒载体对DC进行基因修饰的可行性。特别是用腺病毒载体，我们可以将基因转导到60%以上的单核细胞来源的树突状细胞。利用这些载体，我们还在小鼠模型中表明，通过基因修饰的DC表达包括IL-10、病毒IL-10、IL-12等分子在内的细胞因子，可以调节体内和体外的免疫反应。此外，我们还发现，体内电穿孔Flt3-L基因表达的Flt3-L可以调节宿主体内树突状细胞的成熟、增殖和动员。这些结果有力地表明，DC对免疫反应有很强的影响，基因治疗可能是调节免疫反应的有效途径之一，特别是在体内。这一策略可能会在未来几年应用于癌症治疗。