Analysis of immune response against cancer, which may lead to establishment of WT1 peptide-based immunotherapy for the conventional treatment-resistant malignancies in the respiratory medicine field

• Project/Area Number: 15K09173
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Osaka University
• Principal Investigator: OKA YOSHIHIRO 大阪大学, 医学系研究科, 寄附講座教授 (20273691)
• Co-Investigator(Kenkyū-buntansha): 武田 吉人 大阪大学, 医学系研究科, 助教 (40452388) ; 大塚 倫之 大阪大学, 医学部附属病院, 特任助教(常勤) (20730576)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: WT1 / ペプチドワクチン / 癌抗原 / 癌免疫療法 / 胸部悪性腫瘍 / 免疫療法 / 胸腺悪性腫瘍 / バイオマーカー / 肺癌 / 胸腺腫瘍 / 癌免疫動態

Outline of Final Research Achievements

Analysis of immune response against cancer, focused on cancer antigen WT1-specific immune response, was performed, aiming at the development of WT1 peptide-based immunotherapy for malignancies including those in the respiratory medicine field.
We succeeded in gene cloning of T cell receptor of mouse WT1-specific cytotoxic T lymphocytes. This achievement provided the molecular basis for the mouse in vivo experiment system to analyze WT1-specific immunity, which we had established previously. Based on cDNA microarray analysis of blood samples, Syndecan-4 was shown to be a biomarker to predict clinical outcome of patients with glioblastoma multiforme treated by WT1 vaccine. It was shown that WT1 peptide vaccination induces not only WT1-specific cellular immunity but also WT1-specific antibody. Successful results of clinical studies of WT1 peptide vaccine, including those for thymic malignancies, pancreas cancer, and acute myeloid leukemia, were obtained.

Research Products

• [Journal Article] WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies (2018)
  • Author(s): Oji Y、Inoue M、Takeda Y、Hosen N、Shintani Y、Kawakami M、Harada T、Murakami Y、Iwai M、Fukuda M、Nishida S、Nakata J、Nakae Y、Takashima S、Shirakata T、Nakajima H、Hasegawa K、Kida H、Kijima T、Morimoto S、Fujiki F、Tsuboi A、Morii E、Morita S、Sakamoto J、Kumanogoh A、Oka Y、Okumura M、Sugiyama H
  • Journal Title: International Journal of Cancer Volume: 142 Issue: 11 Pages: 2375-2382
  • DOI: 10.1002/ijc.31253
  • Peer Reviewed / Open Access
• [Journal Article] Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study. (2018)
  • Author(s): Nishida S, Ishikawa T, Egawa S, Koido S, Yanagimoto H, Ishii J, Kanno Y, Kokura S, Yasuda H, Oba MS, Sato M, Morimoto S, Fujiki F, Eguchi H, Nagano H, Kumanogoh A, Unno M, Kon M, Shimada H, Ito K, Homma S, Oka Y, Morita S, Sugiyama H.
  • Journal Title: Cancer Immunol Res. Volume: 6 Issue: 3 Pages: 320-331
  • DOI: 10.1158/2326-6066.cir-17-0386
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Wilms’ tumor gene 1 (WT1) peptide vaccine therapy for hematological malignancies: from CTL epitope identification to recent progress in the clinical studies including a cure-oriented strategy. (2017)
  • Author(s): Oka Y., Tsuboi A., Nakata J., Nishida S., Hosen N., Kumanogoh A., Oji Y., Sugiyama H.
  • Journal Title: Oncol Res Treat. Volume: 40 Issue: 11 Pages: 682-690
  • DOI: 10.1159/000481353
  • Peer Reviewed / Open Access
• [Journal Article] Wilms tumour 1 peptide vaccine as a cure-oriented post-chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse. (2017)
  • Author(s): Nakata J, Nakae Y, Kawakami M, Morimoto S, Motooka D, Hosen N, Fujiki F, Nakajima H, Hasegawa K, Nishida S, Tsuboi A, Oji Y, Oka Y, Kumanogoh A, Sugiyama H.
  • Journal Title: Br J Haematol. Volume: XX Issue: 2 Pages: 287-290
  • DOI: 10.1111/bjh.14768
  • Peer Reviewed / Open Access
• [Journal Article] Syndecan-4 as a biomarker to predict clinical outcome for glioblastoma multiforme treated with WT1 peptide vaccine (2016)
  • Author(s): Takashima S, Oka Y, Fujiki F, Morimoto S, Nakajima H, Nakae Y, Nakata J, Nishida S, Hosen N, Tatsumi N, Mizuguchi K, Hashimoto N, Oji Y, Tsuboi A, Kumanogoh A, Sugiyama H
  • Journal Title: Future Sci OA Volume: FSO96 Issue: 4
  • DOI: 10.4155/fsoa-2015-0008
  • Peer Reviewed / Open Access
• [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] An essential role of the avidity of T-cell receptor in differentiation of self-antigen-reactive CD8+ T cells (2016)
  • Author(s): Kondo K, Fujiki F, Nakajima H, Yatsukawa E, Morimoto S, Tatsumi N, Nishida S, Nakata J, Oka Y, Tsuboi A, Hosen N, Oji Y, Sugiyama H
  • Journal Title: Journal of Immunotherapy Volume: 39 Issue: 3 Pages: 127-139
  • DOI: 10.1097/cji.0000000000000114
  • Peer Reviewed / Open Access
• [Journal Article] Feasibility of cancer immunotherapy with WT1 peptide vaccination for solid and hematological malignancies in children (2016)
  • Author(s): Sawada A, Inoue M, Kondo O, Yamada-Nakata K, Ishihara T, Kuwae Y, Nishikawa M, Ammori Y, Tsuboi A, Oji Y, Koyama-Sato M, Oka Y, Yasui M, Sugiyama H, Kawa K
  • Journal Title: Pediatric Blood ＆ Ｃancer Volume: 63 Issue: 2 Pages: 234-241
  • DOI: 10.1002/pbc.25792
  • Peer Reviewed
• [Presentation] 急性骨髄性白血病に対するWT1ワクチン療法の進捗 (2017)
  • Author(s): 中田 潤、中江吉希、川上 学、岡 芳弘 et al
  • Organizer: 第9回血液疾患免疫療法学会学術集会
• [Presentation] 切除不能進行膵臓癌に対するゲムシタビン併用HLA拘束性WT1ペプチドワクチン療法で誘導されたWT1特異的CTLの免疫学的機能解析 (2017)
  • Author(s): 森本創世子、西田純幸、岡 芳弘、杉山治夫ら
  • Organizer: 第21回日本がん免疫学会学術総会
• [Presentation] An open-label phase II randomized trial of WI1 peptide vaccine plus gemcitabine for advanced pancreatic cancer. (2016)
  • Author(s): Ishikawa T., Nishida S., Egawa S., Koido S., Ishii J., Kanno Y., Yanagimoto H., Kokura S., Morimoto S., Oba M.S., Oka Y., Sugiyama H.
  • Organizer: 第75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: 2016-10-06
• [Presentation] 急性骨髄性白血病に対するWT1ワクチン療法 (2016)
  • Author(s): 中田 潤、中江吉希、川上 学、森本創世子、藤木文博、中島博子、西田純幸、保仙直毅、坪井昭博、尾路祐介、岡 芳弘、杉山治夫
  • Organizer: 第8回血液疾患免疫療法学会学術集会
  • Place of Presentation: 北海道大学医学部学友会館「フラテ」、札幌市
  • Year and Date: 2016-09-03
• [Presentation] Randamized phase II study of WT1 peptide vaccine plus gemcitabine for advanced pancreatic ductal adenocarcinoma (PDAC): Clinical efficacy and immune response. (2016)
  • Author(s): Nishida S., Ishikawa T., Kokura S., Egawa S., Koido S., Yasuda H., Yanagimoto H., Ishii J., Kanno Y., Oba M.S., Sato M., Morimoto S., Eguchi H., Nagano H., Homma S., Oka Y., Morita S., Sugiyama H.
  • Organizer: 2016 ASCO Annual Meeting
  • Place of Presentation: McCormick Place I、Chicago、Illiois、USA
  • Year and Date: 2016-06-05
  • Int'l Joint Research
• [Presentation] WT1 peptide IgG autoantibody: a predictive marker for WT1 peptide-based immunotherapy for glioblastoma. (2015)
  • Author(s): 岩井美樹、尾路祐介、村上由衣、橋本直哉、坪井昭博、保仙直樹、西田純幸、中田 潤、中島博子、岡 芳弘、吉峰俊樹、杉山治夫
  • Organizer: 第7４回日本癌学会学術集会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Book] Immunotherapy of Cancer (Chapter 12 ) WT1 Peptide Vaccine for the Treatment of Malignancies: Its Development, Recent Progress, and Future Perspectives (2016)
  • Author(s): Oka Y, Tsuboi A, Nakajima H, Fujiki F, Nishida S, Morimoto S, Nakata J. Nakae Y, Takashima S, Tatsumi N, Hosen N, Oji Y, Sugiyama H.
  • Total Pages: 27
  • Publisher: Springer