Optimization of cytokine gene therapy based on the regulation of transcription/translation, pharmacokinetics, and cellular response.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390008
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: Kyoto University
• Principal Investigator: TAKAKURA Yoshinobu 京都大学, 薬学研究科(研究院), 教授 (30171432)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Makiya 京都大学, 大学院薬学研究科, 准教授 (40273437) ; TAKAHASHI Yuki 京都大学, 大学院薬学研究科, 助教 (00547870)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ドラッグデリバリー / 遺伝子治療 / インターフェロン / IDO-1 / 腫瘍組織関連マクロファージ / 抗原特異的免疫応答

Outline of Final Research Achievements

The goal of the present study was the development of effective cancer therapy by gene transfer of interferon -γ(IFN-γ). For this goal, it was hypothesized that IDO-1, an IFN-γ-induced immunosuppressive molecule, and tumor-associated macrophage (TAM) might hinder anti-tumor effect of IFN-γ. Base on this hypothesis, the role of these factors in the IFN-γ cancer gene therapy was investigated. We found that TAM reduced the anti-tumor effect of IFN-γ and depletion of TAM restored it. On the other hand, IDO-1 hardly affected the anti-tumor effect of IFN-γ. In the process of these investigations, we also found that persistent transgene expression of antigenic protein induced the transgene-specific immune response, which removed the transgene-expressing cells.

Free Research Field

生物薬剤学