Overcoming immune escape in WT1 peptide vaccination for malignant glioma

• Project/Area Number: 25462257
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Research Institute, Osaka Medical Center for Maternal and Child Health (2015-2016); Osaka University (2013)
• Principal Investigator: Chiba Yasuyoshi 地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), その他部局等, 脳神経外科・医長 (90533795)
• Co-Investigator(Kenkyū-buntansha): 坪井 昭博 大阪大学, 医学系研究科, 寄附講座教授 (10372608) ; 橋本 直哉 京都府立医科大学, 医学(系)研究科(研究院), 教授 (90315945) ; 高野 浩司 大阪大学, 医学系研究科, 招へい教員 (90649203)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: WT1 / peptide vaccine / immunotherapy / glioma / GBM / HLA class 1 / PD-1 / PD-L1 / ペプチドワクチン / グリオーマ / MDSC / IDO / メチオニン-PET / TSPO-PET / 神経膠腫 / がん免疫療法 / 免疫逃避 / 膠芽腫 / 腫瘍浸潤リンパ球 / HLA class1

Outline of Final Research Achievements

In this work, we tried to elucidate the mechanism of immune escape of tumor cells in WT1 peptide vaccination from human specimens and animal experiments. In a study using a human specimen, it was suggested that when WT1 peptide vaccination is administered, tumor cells decrease the expression of WT1 and HLA class 1 and secrete TGFβ, thereby escape attack by immunity. In the animal experiments, it was found that in the WT1 peptide vaccine group, killer T cells infiltrate into the tumor to exert antitumor effect and the survival time was prolonged, and methionine PET is excellent as a judgment of its effect.

Research Products

• [Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. (2016)
  • Author(s): Oji Y, Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Elisseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
  • Journal Title: Int J Cancer. Volume: 139 Issue: 6 Pages: 1391-401
  • DOI: 10.1002/ijc.30182
  • Peer Reviewed / Open Access
• [Journal Article] Introduction of High Throughput Magnetic Resonance T2-Weighted Image Texture Analysis for WHO Grade 2 and 3 Gliomas. (2016)
  • Author(s): Kinoshita M, Sakai M, Arita H, Shofuda T, Chiba Y, Kagawa N, Watanabe Y, Hashimoto N, Fujimoto Y, Yoshimine T, Nakanishi K, Kanemura Y.
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0164268-e0164268
  • DOI: 10.1371/journal.pone.0164268
  • Peer Reviewed / Open Access
• [Journal Article] Wilms' tumor 1 is involved in tumorigenicity of glioblastoma by regulating cell proliferation and apoptosis. (2014)
  • Author(s): Kijima N, Hosen N, Kagawa N, Hashimoto N, Kinoshita M, Oji Y, Sugiyama H, Yoshimine T.
  • Journal Title: Anticancer Res Volume: 34 Pages: 61-67
  • Peer Reviewed
• [Journal Article] HLA-DPB1*05: 01-restricted WT1332-specific TCR-transduced CD4+ T lymphocytes display a helper activity for WT1-specific CTL induction and a cytotoxicity against leukemia cells. (2013)
  • Author(s): Lin Y, Fujiki F, Katsuhara A, Oka Y, Tsuboi A, Aoyama N, Tanii S, Nakajima H, Tatsumi N, Morimoto S, Tamanaka T, Tachino S, Hosen N, Nishida S, Oji Y, Kumanogoh A, Sugiyama H.
  • Journal Title: J Immunother. Volume: 36（3） Issue: 3 Pages: 159-70
  • DOI: 10.1097/cji.0b013e3182873581
  • Peer Reviewed
• [Journal Article] Functional human Th17 clones with WT1-specific helper activity. (2013)
  • Author(s): Tachino S, Fujiki F, Oka Y, Tsuboi A, Morimoto S, Lin YH, Tamanaka T, Kondo K, Nakajima H, Nishida S, Hosen N, Oji Y, Kumanogoh A, Sugiyama H.
  • Journal Title: Cancer Immunol Immunother. Volume: 62（4） Issue: 4 Pages: 801-10
  • DOI: 10.1007/s00262-012-1385-3
  • Peer Reviewed
• [Presentation] WT1ペプチドワクチン療法の治療効果判定：18F-DPA-714 PETの有用性 (2016)
  • Author(s): 高野浩司、石橋愛、渡部直史、中島博子、千葉泰良、阿知波孝宗、横田千里、福永貴典、福屋章悟、永野大輔、有田英之、香川尚己、藤本康倫、畑澤順、杉山治夫、橋本直哉、吉峰俊樹
  • Organizer: 日本脳腫瘍学会
  • Place of Presentation: 甲府
  • Year and Date: 2016-12-04
• [Presentation] マウスグリオーマ脳腫瘍モデルを用いたWT1ペプチドワクチン療法の検討 (2015)
  • Author(s): 高野浩司、千葉泰良、中島博子、福永貴典、福屋章悟、永野大輔、平山龍一、有田英之、香川尚己、橋本直哉、杉山治夫、吉峰俊樹
  • Organizer: 第33回日本脳腫瘍学会
  • Place of Presentation: グランドプリンスホテル京都
  • Year and Date: 2015-12-06
• [Presentation] WT1 peptide IgG antibody as a predictive marker of WT1 peptide vaccine immunotherapy (2015)
  • Author(s): Yusuke Oji, Naoya Hashimoto, Akihiro Tsuboi, Yui Murakami, Miki Iwai, Naoki Kagawa, Yasuyoshi Chiba et.al.
  • Organizer: The 8th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: KBS Kyoto Hall, Kyoto, Japan
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] New challenge of WT1 peptide vaccination for malignant glioma (2015)
  • Author(s): Akihiro Tsuboi, Naoya Hashimoto, Naoki Kagawa, Yasuyoshi Chiba, Manabu Kinoshita, Noriyuki Kijima, Yoshihiro Oka, Shuichi Izumoto, Norio Arita, Soyoko Morimoto, Fumihiro Fujiki, Hiroko Nakajima, Naoki Hosen, Yusuke Oji, Sumiyuki Nishida, Satoshi Morita, Junichi Sakamoto, Toshiki Yoshimine, Haruo Sugiyama
  • Organizer: The 8th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: KBS Kyoto Hall, Kyoto, Japan
  • Year and Date: 2015-11-19
  • Int'l Joint Research
• [Presentation] 神経膠腫に対するWT1ペプチドワクチン療法の新展開 (2015)
  • Author(s): 橋本 直哉, 坪井 昭博, 香川 尚己, 千葉 泰良, 木嶋 教行, 木下 学, 有田 英之, 平山 龍一, 永野 大輔, 高野 浩司, 福屋 章悟, 福永 貴典, 岡 芳弘, 尾路 祐介, 杉山 治夫, 吉峰 俊樹
  • Organizer: 第74回日本脳神経外科学会学術総会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2015-10-14
• [Presentation] 初発膠芽腫に対するテモゾロミド併用WT1ペプチドワクチン療法
  • Author(s): 橋本直哉、坪井昭博、千葉泰良、香川尚己、泉本修一、平山龍一、岡芳弘、尾路祐介、吉峰俊樹、杉山治夫
  • Organizer: 第17回がん免疫学会総会
  • Place of Presentation: ANAクラウンプラザホテル宇部(山口）
• [Presentation] WT1 peptide vaccination for newly diagnosed glioblastomas; phase I clinical trial of combination with temozolomide
  • Author(s): Naoya Hashimoto,Yasuyoshi Chiba,Noriyuki Kijima,Manabu Kinoshita,Naoki kagawa,Akihiro Tsuboi,Yoshihiro Oka,Yusuke Oji,Haruo Sugiyama,Toshiki Yoshimine
  • Organizer: 15th WFNS World Congress of Neurosurgery (WFNS2013)
  • Place of Presentation: Seoul（Korea）
• [Presentation] 再発悪性グリオーマに対するWT1ペプチドワクチン療法後の腫瘍浸潤リンパ球と免疫逃避
  • Author(s): 千葉泰良、橋本直哉、坪井昭博、岡芳弘、香川尚己、尾路祐介、吉峰俊樹、杉山治夫
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] 初発膠芽腫に対するテモゾロミド併用WT1ペプチドワクチン療法 第1相臨床試験
  • Author(s): 坪井昭博、橋本直哉、香川尚己、千葉泰良、泉本修一、岡芳弘、尾路祐介、保仙直毅、西田純幸、森本創世子、吉峰俊樹、杉山治夫
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] グリオーマに対するペプチドワクチン療法の現状と展望
  • Author(s): 橋本直哉
  • Organizer: 第26回神奈川脳腫瘍フォーラム
  • Place of Presentation: 横浜（神奈川）
  • Invited
• [Presentation] 再発悪性グリオーマに対するWT1ペプチドワクチン療法後の免疫逃避機構
  • Author(s): 千葉泰良、橋本直哉、坪井昭博、香川尚己、平山龍一、尾路祐介、岡芳弘、杉山治夫、吉峰俊樹
  • Organizer: 第72回日本脳神経外科学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川）
• [Presentation] Immune escape in human malignant gliomas after WT1 peptide vaccination
  • Author(s): Yasuyoshi Chiba, Naoya Hashimoto, Naoki Kagawa, Ryuuichi Hirayama, Akihiro Tsuboi, Yuusuke Oji, Yoshihiro Oka, Haruo Sugiyama, Toshiki Yoshimine
  • Organizer: SNO 4th Quadrennial Meeting of the World Federation of Neuro-Oncology
  • Place of Presentation: San Francisco（ＵＳＡ）
• [Presentation] A direct comparison of response assessments in a phase II clinical trial of WT1 peptide vaccination; Macdonald, RECIST and RANO criteria
  • Author(s): Naoya Hashimoto, Yasuyoshi Chiba, Akihiro Tsuboi, Manabu Kinoshita, Ryuichi Hirayama, Naoki Kagawa, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama, Toshiki Yoshimine
  • Organizer: SNO 4th Quadrennial Meeting of the World Federation of Neuro-Oncology
  • Place of Presentation: San Francisco（ＵＳＡ）
• [Presentation] WT1ペプチドワクチン療法におけるMRIを用いた画像評価法の検討
  • Author(s): 千葉泰良、橋本直哉、坪井昭博、香川尚己、平山龍一、尾路祐介、岡芳弘、杉山治夫、吉峰俊樹
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: フェニックスシーガイアリゾート（宮崎）
• [Presentation] グリオーマのWT1ペプチドワクチン療法；バイオマーカーの探索と免疫的応答
  • Author(s): 橋本直哉、坪井昭博、千葉泰良、森本創世子、木下学、香川尚己、平山龍一、高野浩司、永野大輔、福屋章悟、岡芳弘、尾路祐介、杉山治夫、吉峰俊樹
  • Organizer: 第31回日本脳腫瘍学会学術集会
  • Place of Presentation: フェニックスシーガイアリゾート（宮崎）
• [Presentation] 初発悪性神経膠腫に対するテモゾロミドとWT1ペプチドワクチン併用療法
  • Author(s): 坪井 昭博 、橋本 直哉、香川 尚己、千葉 泰良、吉峰 俊樹
  • Organizer: 第17回WT1ペプチド癌免疫療法研究会
  • Place of Presentation: 大阪大学医学部（大阪）
• [Book] Wilms Tumor Chapter 15. (2016)
  • Author(s): Kijima N, Hashimoto N, Chiba Y, Fujimoto Y, Sugiyama H, Yoshimine T.
  • Total Pages: 294
  • Publisher: Codon Publications