HSV-1 amplicon as a novel vector for gene transfer into refractory tumors

• Project/Area Number: 24501351
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Nagoya University
• Principal Investigator: GOSHIMA Fumi 名古屋大学, 医学(系)研究科(研究院), 助教 (70201499)
• Co-Investigator(Kenkyū-buntansha): KIMURA Hiroshi 名古屋大学, 大学院医学系研究科, 教授 (30303621) ; KAMAKURA Maki 名古屋大学, 医学(系)研究科(研究院), その他 (80437003)
• Research Collaborator: ESAKI Shinichi 名古屋市立大学, 大学院医学研究科, 助教 (20620983)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子治療 / ウイルス / アンプリコン / 癌

Outline of Final Research Achievements

We made an HSV amplicon expressing murine GM-CSF to strengthen anti-tumor immune response for the treatment of ovarian cancer with intraperitoneal dissemination. Intraperitoneal injection of mGM-CSF amplicon prolonged survival and decreased intraperitoneal dissemination. Immunohistochemical staining revealed the infiltration of CD4- and CD8-positive cells into the peritoneal tumors. Murine splenic cells after each treatment were stimulated with HM-1 cells, and the strongest immune response was observed in the mice that received mGM-CSF amplicon injections. Now we have made an HSV amplicon expressing murine IL-2 and confirmed expression of IL2 in the infected cells.

Research Products

• [Journal Article] Oncolytic viral therapy with a combination of HF10, a herpes simplex virus type 1 variant and granulocyte-macrophage colony-stimulating factor for murine ovarian cancer. (2014)
  • Author(s): Goshima F, Esaki S, Luo C, Kamakura M, Kimura H, Nishiyama Y.
  • Journal Title: Int J Cancer. Volume: 134 Pages: 2865-2877
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Oncolytic viral therapy with a combination of HF10, a herpes simplex virus type 1 variant and granulocyte-macrophage colony-stimulating factor for murine ovarian cancer (2014)
  • Author(s): Goshima F1, Esaki S, Luo C, Kamakura M, Kimura H, Nishiyama Y
  • Journal Title: Int J Cancer Volume: 15 Issue: 12 Pages: 2865-77
  • DOI: 10.1002/ijc.28631
  • Peer Reviewed
• [Journal Article] Enhanced antitumoral activitiy of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models. (2012)
  • Author(s): Esaki S, Goshima F, Kimura H, Murakami S, Nishiyama Y.
  • Journal Title: International Journal of Cancer Volume: 132 Issue: 7 Pages: 1592-601
  • DOI: 10.1002/ijc.27823
  • Peer Reviewed
• [Presentation] マウス悪性黒色腫両側皮下モデルにおけるダカルバジンの併用療法 (2014)
  • Author(s): 田中るい、五島典、江崎伸一、村田貴之、渡辺大輔、西山幸廣、木村宏
  • Organizer: ウイルス学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] マウス卵巣癌腹腔播種モデルにおけるHSV-1 HF10とマウスGM-CSFアンプリコンを用いた抗腫瘍効果の検討 (2013)
  • Author(s): 五島典、江崎伸一、田中るい、村田貴之、渡辺大輔、木村宏、西山幸廣
  • Organizer: 第61回日本ウイルス学会学術集会
  • Place of Presentation: 神戸国際会議場(神戸市）
• [Presentation] マウス卵巣癌腹膜播種モデルにおけるHSV-1 HF10とマウスGM-CSFアンプリコンを用いた治療効果の検討 (2012)
  • Author(s): 五島典、江崎伸一、武藤義文、岩田誠子、鎌倉真紀、渡辺大輔、木村宏、西山幸廣
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: 大阪（グランキューブ大阪）