Development of WT1 peptide vaccine for ovarian cancer and analyses of WT1-CTLs

• Project/Area Number: 16K11136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Osaka University
• Principal Investigator: Nishida Sumiyuki 大阪大学, 医学系研究科, 助教 (00403189)
• Research Collaborator: Morimoto Soyoko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: がん免疫療法 / 卵巣がん / がんワクチン / WT1 / 抗原特異的T細胞 / 卵巣癌 / WT1ペプチドワクチン / 婦人科腫瘍学

Outline of Final Research Achievements

I conducted the clinical study of WT1 peptide vaccine for advanced ovarian cancer and performed the time course of WT1-specific immune response induced by WT1 vaccine and their phenotypical and functional assessments.
I found the association between the prolonged disease-free survival and the induction of WT1-specific immune response. Especially, 1) a longer maintenance of WT1-CTLs 2) the effector phenotype was induced first, and then the memory phenotype emerged dominantly. Patient who had exhibited these characteristics of WT1-CTLs induced by WT1 vaccine had 2 year or longer disease free-survival.

Academic Significance and Societal Importance of the Research Achievements

卵巣がんは、婦人科がんの中でも最も予後不良ながんである。近年、他のがん種では免疫チェックポイント阻害治療が期待されているが、卵巣がんにおいては、これら単独療法では有効性が示されていない。がんワクチンや免疫アジュバントなどその他のがん免疫療法との組合せによる相乗効果が期待される。
本研究は、卵巣癌を対象にWT1を標的にしたがんワクチン療法を実施し、本治療法の臨床的効果と抗原特異的免疫誘導との関連性を明らかにした。今回の結果は、卵巣がんに対する集学的がん免疫療法の今後の開発に寄与できる可能性がある。

Research Products

• [Journal Article] A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma (2018)
  • Author(s): Tsuboi A, Hashimoto N, Fujiki F, Morimoto S, Kagawa N, Nakajima H, Hosen N, Nishida S, Nakata J, Morita S, Sakamoto J, Oji Y, Oka Y, Sugiyama H
  • Journal Title: Cancer Immunology, Immunotherapy Volume: 68(2) Issue: 2 Pages: 331-340
  • DOI: 10.1007/s00262-018-2274-1
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity (2018)
  • Author(s): Morimoto Soyoko、Fujiki Fumihiro、Kondo Kenta、Nakajima Hiroko、Kobayashi Yoshiki、Inatome Miki、Aoyama Nao、Nishida Yuya、Tsuboi Akihiro、Oka Yoshihiro、Nishida Sumiyuki、Nakata Jun、Hosen Naoki、Oji Yusuke、Sugiyama Haruo
  • Journal Title: Oncotarget Volume: 9 Issue: 75 Pages: 34132-34141
  • DOI: 10.18632/oncotarget.26139
  • Peer Reviewed / Open Access
• [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 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] 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] Cancer Immunotherapy targeting WT1: Designing a protocol for WT1 peptide-based cancer vaccine. (2016)
  • Author(s): Sumiyuki Nishida, Haruo Sugiyama
  • Journal Title: Springer Protocols Volume: 1467 Pages: 221-232
  • DOI: 10.1007/978-1-4939-4023-3_19
  • ISBN: 9781493940219, 9781493940233
• [Journal Article] Wilms tumor 1 peptide vaccination after hematopoietic stem cell transplant in leukemia patients. (2016)
  • Author(s): Hosen N, Maeda T, Hashii Y, Tsuboi A, Nishida S, Nakata J, Oji Y, Oka Y, Sugiyama H.
  • Journal Title: Stem Cell Investig. Volume: 3 Pages: 90-90
  • DOI: 10.21037/sci.2016.11.08
  • Peer Reviewed
• [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
• [Presentation] Randomized phases II study of WT1 peptide vaccine in combination with gemcitabine for advanced pancreaticcancer: association between clinical efficacy and immune response in metastatic pancreatic cancer patinets. (2018)
  • Author(s): Sumiyuki Nishida, Soyoko Morimoto, Yoshihiro Oka, Shinichi Egawa, Takeshi Ishikawa, Shigeo Koido, Hiroaki Yasuda, Hiroaki Yanagimoto, Jun Ishii, Yoshihide Kanno, Atsushi Kumanogoh, Satoshi Morita, Haruo Sugiyama
  • Organizer: 9th International Conference on WT1 in Human Neoplasia
  • Int'l Joint Research
• [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity. (2018)
  • Author(s): Soyoko Morimoto, Fumihiro Fujiki, Kenta Kondo, Hiroko Nakajima, Yoshiki Kobayashi, Miki Inatome, Nao Aoyama, Yuya Nishida, Akihiro Tsuboi, Yoshihiro Oka, Sumiyuki Nishida, Jun Nakata, Naoki Hosen, Yusuke Oji, Haruo Sugiyama
  • Organizer: 9th International Conference on WT1 in Human Neoplasia
  • Int'l Joint Research
• [Presentation] Immunomonitoring fo Rare Cancer Patinets Treated with WT1 Trio Peptide-based Cancer Immunotherapy (2018)
  • Author(s): Yusuke Oji, Miki Iwai, Sae Hayashi, Naoki Kagawa, Hideyuki Arita, Yasushi Shintani, Yoshito Takeda, Eiichi Morii, Kenichiro Hamada, Kenzo Shimazu, Motoyuki Suzuki, Hiroko Nakajima, Fumihiro Fujiki, Rin Imanishi, Kana Hasegawa, Soyoko Morimoto, Jun Nakata, Sumiyuki NIshida, et al
  • Organizer: 9th International Conference on WT1 in Human Neoplasia
  • Int'l Joint Research
• [Presentation] 進行膵癌に対するWT1ペプチドワクチン併用化学療法無作為比較第II相試験 (2017)
  • Author(s): 江川 新一、石川 剛、西田 純幸
  • Organizer: 第103回日本消化器病学会総会
• [Presentation] 切除不能進行膵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、小井戸 薫雄、江川 新一、石川 剛、石井 淳、菅野 良秀、柳本 泰明、江口 英利、中田 潤、保仙 直毅、坪井 昭博、長谷川 加奈、中島 博子、藤木 文博、尾路 祐介、熊ノ郷 淳、岡 芳弘、杉山 治夫
  • Organizer: 第21回 日本がん免疫学会総会
• [Presentation] An open-label phase II randomized trial of WT1 peptide vaccine plus gemcitabine for advanced pancreatic cancer (2016)
  • Author(s): Takeshi Ishikawa, Sumiyuki Nishida, Shinichi Egawa, Shigeo Koido, Jun Ishii, Yoshihide Kanno, Hiroaki Yanagimoto, Satoshi Kokura, Soyoko Morimoto, Mari S. Oba, Yoshihiro Oka, and Haruo Sugiyama
  • 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
  • Year and Date: 2016-10-06
• [Presentation] 進行膵癌に対するゲムシタビン併用WT1ワクチン療法ランダム化第II相臨床試験：臨床効果と抗原特異的免疫反応の評価 (2016)
  • Author(s): 西田 純幸、石川 剛、江川 新一、小井戸 薫雄、森本 創世子、石井 淳、菅野 良秀、柳本 泰明、大庭 真梨、古倉 聡、本間 定、島田 英昭、森田 智視、岡 芳弘、杉山 治夫
  • Organizer: 第20回日本がん免疫学会総会
  • Place of Presentation: 大阪国際交流センター、大阪
  • Year and Date: 2016-07-27
• [Presentation] Randomized phases II study of WT1 peptide vaccine plus gemcitabine for advanced pancreatic ductal adenocarcinoma (PDAC): Clinical efficacy and immune response (2016)
  • Author(s): Sumiyuki Nishida, Takeshi Ishikawa, Satoshi Kokura, Shinichi Egawa, Shigeo Koido, Hiroaki Yasuda, Hiroaki Yanagimoto, Jun Ishii, Yoshihide Kanno, Mari S. Ohba, Maho Sato, Soyoko Morimoto, Hidetoshi Eguchi, Hiroaki Nagano, Sadamu Homma, Yoshihiro Oka, Satoshi Morita, and Haruo Sugiyama
  • Organizer: ASCO Annual Meeting 2016
  • Place of Presentation: McCormick Place, Chicago, USA
  • Year and Date: 2016-06-03
  • Int'l Joint Research