Manipulation of tumor microenvironment by cytokine gene transfection enhances dendritic cell-based immunotherapy

2015 Fiscal Year Final Research Report

• Project/Area Number: 23380174
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Osaka Prefecture University
• Principal Investigator: SUGIURA KIKUYA 大阪府立大学, 生命環境科学研究科(系), 准教授 (30171143)
• Co-Investigator(Kenkyū-buntansha): AKAZAWA Takashi 地方独立行政法人大阪府立病院機構大阪府立成人病センター, 研究所、腫瘍免疫部門, 主任研究員 (80359299) ; HATOYA Shingo 大阪府立大学, 生命環境科学研究科, 准教授 (40453138) ; INABA Toshio 大阪府立大学, 生命環境科学研究科, 教授 (00137241)
• Co-Investigator(Renkei-kenkyūsha): KOUNO Kenji 大阪府立大学, 工学研究科, 教授 (90215187)
• Project Period (FY): 2011-04-01 – 2016-03-31
• Keywords: 腫瘍免疫治療 / 遺伝子導入 / 人工ベクター / DC40リガンド / インターフェロンγ / 樹状細胞

Outline of Final Research Achievements

Using a novel synthetic vector of a cationic lipid bound with pH-sensitive liposomes, we transfected cytokine genes into tumor cells to manipulate tumor microenvironment for facilitating dendritic cell (DC) therapy. The efficiency of transfection into the LM8 osteosarcoma growing in syngeneic C3H mice was about 10% by both intratumor (i.t.) and intravenous (i.v.) injection of the vector enclosing GFP-expression plasmid. Therapeutic experiments were performed to inhibit LM8 growth by injection of the interferon (IFN) γ-vector or the CD40L-vector, followed by i.t. injection of the DCs presenting the LM8 antigens. Growth of the tumor was significantly suppressed by the treatment of the IFNγ-plasmid vector and the CD40L-plasmid vector. The CD40L-vector treatment led to significantly improved survival. These results indicate that gene transfection of the cytokine genes manipulate the tumor microenvironment effectively and significantly improve DC-based tumor immunotherapy.

Free Research Field

免疫学