Development of novel cancer immunotherapy based on memory-oriented TCR

• Project/Area Number: 17K07216
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: Morimoto Soyoko 大阪大学, 医学系研究科, 寄附講座助教 (10649023)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: メモリー / TCR functional avidity / WT1 / TCR avidity / T細胞受容体 / memory / TCR

Outline of Final Research Achievements

In our previous reports, we demonstrated that induction and maintain of tumor-antigen specific-memory T cells in vivo needed to successful treatment of cancer immunotherapy and that TCR avidity have played an essential role in differentiation of naive T cells to memory T cells. To evaluate accurately of TCR avidity, we tried to establish the platform cell that could reflect the function of TCR-transduced T cells. TCR avidity evaluated by TCR-transduced platform cells correlated with cytokine production, cell proliferation, and cytotoxic activity of TCR-transduced T cells. These results showed that the platform cell was a novel and stable tool for the efficient and precise evaluation of the functional avidity of isolated and transduced TCRs in developing TCR-base immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

近年の技術的発展に伴い、TCR遺伝子治療に用いるTCRの選択肢が大幅に広がった。しかしながら、治療に最良のTCRを選択する方法が無かった。本研究で作製したplatform細胞を用いることで、簡便かつ正確にTCR導入T細胞の機能を反映したTCR avidityを評価でき、最良のTCR選択が可能となる。さらに、platform細胞作製に用いた実験系を応用することで、TCR分化決定因子としてのTCR signalやそれに伴う遺伝子発現の差を評価することも可能となる。これは、TCR遺伝子治療のみならずがん免疫療法全般に対して治療効果改善の一端を担う可能性を大いに示唆する。

Research Products

• [Journal Article] Immune adjuvant therapy using Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity assessments. (2019)
  • Author(s): Nishida S, Tsuboi A, Tanemura A, Ito T, Nakajima H, Shirakata T, Morimoto S, Fujiki F, Hosen N, Oji Y, Kumanogoh A, Kawase I, Oka Y, Azuma I, Morita S, Sugiyama H.
  • Journal Title: Medicine (Baltimore) Volume: 98 Issue: 33 Pages: e16771-e16771
  • DOI: 10.1097/md.0000000000016771
  • Peer Reviewed / Open Access
• [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] A versatile T cell-based assay to assess therapeutic antigen-specific PD-1-targeted approaches (2018)
  • Author(s): Versteven Maarten、Bergh Johan M.J. Van den、Broos Katrijn、Fujiki Fumihiro、Campillo-Davo Diana、De Reu Hans、Morimoto Soyoko、Lecocq Quentin、Keyaerts Marleen、Berneman Zwi、Sugiyama Haruo、Van Tendeloo Viggo F.I.、Breckpot Karine、Lion Eva
  • Journal Title: Oncotarget Volume: 9 Issue: 45 Pages: 27797-27808
  • DOI: 10.18632/oncotarget.25591
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] 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] 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
• [Presentation] 癌抗原特異的T細胞受容体のfunctional avidityを効率よく正確に評価できるplatform細胞の作製とその応用例 (2019)
  • Author(s): 森本 創世子、藤木 文博、近藤 健太、中島 博子、中田 潤、保仙 直毅、 橋井 佳子 、坪井 昭博、岡 芳弘、尾路 祐介、杉山 治夫
  • Organizer: 日本血液疾患免疫療法学会
• [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity and its application (2019)
  • 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, and Haruo Sugiyama
  • Organizer: International conference on WT1 biology
  • Int'l Joint Research
• [Presentation] 脳腫瘍患者におけるWT1ヘルパーペプチド併用WT1ペプチドワクチン療法の免疫モニタリング解析 (2019)
  • Author(s): 森本 創世子、坪井 昭博、藤木 文博、橋本 直哉、稲留 美希、中島 博子、中田 潤、保仙 直毅、尾路 祐介、岡 芳弘、杉山 治夫
  • Organizer: 日本臨床免疫学会総会
• [Presentation] 癌抗原特異的T細胞受容体のfunctional avidityを効率よく正確に評価できるplatform細胞の作製 (2018)
  • Author(s): 森本創世子
  • Organizer: 第22回日本がん免疫学会総会
• [Presentation] 癌抗原特異的T細胞受容体のfunctional avidityを効率よく正確に評価できるplatform細胞の作製 (2018)
  • Author(s): 森本創世子
  • Organizer: 第46回日本臨床免疫学会総会
• [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity (2018)
  • Author(s): Soyoko Morimoto
  • Organizer: The 9th International Conference on WT1 in Human Neoplasia
  • Int'l Joint Research
• [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
  • Organizer: 第21回日本がん免疫学会総会