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系统，以支持基因治疗的早期临床研究。为了实现这一目标，我们启动了一个过程，以生产腺病毒载体携带白细胞介素-12（Ad-IL-12），用于癌症免疫基因治疗方案，使用树突状细胞（DC）转导IL-12基因。为了促进这个项目，我们开始使用我们独特的设施“治疗载体核心设施（CFTV）”，建立我们自己的生产细胞（293细胞）的主细胞库（MCB）和工作细胞库（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建议进行了我们的项目，并成功地建立了MCB和WCB，并获得了FDA推荐的认证。同时，我们构建了用于制备Ad-IL-12的粘粒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，我们还研究了DCs的功能和操作，DCs是基因转导的靶点，也是我们临床试验中使用的载体，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，可以支持在日本的基因治疗临床协议。

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.