Clinical development of cancer gene therapy using viral vectors

该项目的最终目标是在日本学术界建立一个支持基因治疗早期临床研究的系统。为了实现这一目标，我们启动了一个过程来制造携带白细胞介素-12（Ad-IL-12）的腺病毒载体，用于使用IL-12基因转导的树突状细胞（dc）的癌症免疫基因治疗方案。为了促进这个项目，我们开始使用我们独特的设施，称为“治疗载体核心设施（CFTV）”，制作我们自己的主细胞库（MCB）和生产细胞（293细胞）的工作细胞库（WCB），这些细胞具有美国食品和药物管理局（FDA）要求的质量。我们已经按照最初的计划进行了我们的项目，并成功建立了MCB和WCB，并通过了FDA的推荐认证。同时，我们构建了用于制造Ad-IL-12的cosmid DNA。我们还制定了标准操作程序（sop），以确保最终产品的质量。此外，我们还对作为基因转导靶点和临床试验载体的dc的功能和操作进行了研究，揭示了与临床试验相关的重要信息。这些结果表明，我们现在有一个可行的系统，可以支持日本的基因治疗临床方案。

The final goal of this project is to establish a system in Japanese academia to support early-phase clinical studies of gene therapy. In order to achieve it, we initiated a process to manufacture adenoviral vector carrying Interleukin-12(Ad-IL-12) to be used in cancer immune-gene therapy protocol using dendritic cells(DCs) transduced with IL-12 genes. To facilitate this project, we started, using our unique facility called "Core Facility for Therapeutic Vectors(CFTV)", making our own master cell bank(MCB) and working cell bank(WCB) of producer cells (293 cells) which have qualities required by the Food and Drug Administration(FDA) of the United States. We have carried on our project as initially proposed and successfully established MCB and WCB which are certified as FDA recommended. At the same time, we constructed cosmid DNA which would be used to make Ad-IL-12. We also made Standard Operating Procedures(SOPs) to ensure the quality of the final products. Furthermore, we also studied on the function and manipulation of DCs which are the target of the gene-transduction and the vehicle to be used in our clinical trial, and revealed important information related to the clinical trial. These results suggest that we are now have a viable system which could support gene therapy clinical protocols in Japan.