Anti-tumor immunotherapy in humanized the NOG-MHC double knockout mouse

• Project/Area Number: 26430178
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Shizuoka Cancer Center Research Institute
• Principal Investigator: Iizuka Akira 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (00463183)
• Co-Investigator(Kenkyū-buntansha): 秋山 靖人 静岡県立静岡がんセンター(研究所), その他部局等, 副研究所長 (70222552)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腫瘍免疫 / グリオーマ / マウスモデル / 変異抗原 / 癌精巣抗原

Outline of Final Research Achievements

With the recent success of immune checkpoint inhibitors, T cell dependent tumor immune responses have been demonstrated in clinical studies. But in preclinical studies, immuno-humanized mouse models are associated several limitations, such as long incubation time for hematopoietic stem cell engraftment and the development of xenograft versus host disease (GVHD) in mice injected with human peripheral blood mononuclear cells (hPBMC), so immunological drugs for human tumors could not evaluated in non-human in vivo models. In this study we had the severely immunodeficient mouse strain, MHC class I, class II-deficient NOD/Shi-scid-IL2rγnull (NOG), for build the immuno-humanized mouse model and enabled long term hPBMC and human tumor xenograftment without GVHD to evaluate the antitumor effect of immunomodulatory agent, such as anti-programmed death-1 (PD-1) antibody.

Research Products

• [Journal Article] Antitumor Effect of Programmed Death-1 (PD-1) Blockade in Humanized the NOG-MHC Double Knockout Mouse. (2017)
  • Author(s): Ashizawa T, Iizuka A, Nonomura C, Kondou R, Maeda C, Miyata H, Sugino T, Mitsuya K, Hayashi N, Nakasu Y, Maruyama K, Yamaguchi K, Katano I, Ito M, Akiyama Y.
  • Journal Title: Clinical Cancer Research Volume: 23(1) Issue: 1 Pages: 149-158
  • DOI: 10.1158/1078-0432.ccr-16-0122
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Immunologically augmented skin flap as a novel dendritic cell vaccine against head and neck cancer in a rat model. (2015)
  • Author(s): Inoue K, Saegusa N, Omiya M, Ashizawa T, Miyata H, Komiyama M, Iizuka A, Kume A, Sugino T, Yamaguchi K, Kiyohara Y, Nakagawa M, Akiyama Y.
  • Journal Title: Cancer Sci. Volume: 106 (2) Issue: 2 Pages: 143-150
  • DOI: 10.1111/cas.12586
  • Peer Reviewed / Open Access
• [Journal Article] Novel cancer-testis antigen expression on glioma cell lines derived from high-grade glioma patients. (2014)
  • Author(s): Akiyama Y, Komiyama M, Miyata H, Yagoto M, Ashizawa T, Iizuka A, Oshita C, Kume A, Nogami M, Ito I, Watanabe R, Sugino T, Mitsuya K, Hayashi N, Nakasu Y, Yamaguchi K.
  • Journal Title: Oncol Rep. Volume: 31 Issue: 4 Pages: 1683-1690
  • DOI: 10.3892/or.2014.3049
  • Peer Reviewed / Open Access
• [Presentation] Anti-PD-1 antibody therapy using humanized MHC-dKO NOG mouse (2015)
  • Author(s): Tadashi Ashizawa, Akira Iizuka, Kouji Maruyama, Ken Yamaguchi, Yasuto Akiyama
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: Nagoya Congress Center
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] プロジェクトHOPE（マルチオーミクス解析を用いたがん患者評価)－グリオブラストーマ細胞株における遺伝子解析 (2014)
  • Author(s): 秋山靖人、小宮山優、長嶋剛史、下田勇次、田邉智絵、大浪澄子、大浪俊平、大島啓一、浦上研一、楠原正俊、望月徹、山口建
  • Organizer: 第７３回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(横浜市）
  • Year and Date: 2014-09-26