Control of antigen-specific T-cell-mediated immune response by inhibitory immune receptors and its application to adoptive T-cell therapy

• Project/Area Number: 16H06868
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Nagoya University
• Principal Investigator: Goto Tatsunori 名古屋大学, 医学部附属病院, 病院助教 (20778526)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 抗原特異的T細胞 / PD-1 / PD-L1 / 抗原提示細胞 / 細胞療法

Outline of Final Research Achievements

K562-based artificial APCs, which were transduced with HLA class I molecules, CD80/86 and PD-L1, produced efficient induction of WT1-specific CTLs from T cells in peripheral blood of healthy donors. The autologous leukemia cell-reactive T cells were identified in CD8+PD-1+ T cell populations from peripheral blood of patients with leukemia, and this suggested that PD-1 expression on CD8+ T cells might be a marker for the separation of leukemia-specific T cells. These findings are applicable to T cell immunotherapy in the future.

Research Products

• [Journal Article] Mesenchymal stem cell therapy in hematopoietic stem cell transplantation (2018)
  • Author(s): Goto T, Murata M
  • Journal Title: Rinsho Ketsueki Volume: 59 Issue: 2 Pages: 195-204
  • DOI: 10.11406/rinketsu.59.195
  • NAID: 130006441930
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Successful treatment with allogeneic stem cell transplantation followed by DLI and TKIs for e6a2 BCR-ABL-positive acute myeloid leukaemia: A case report and literature review. (2017)
  • Author(s): Harada Y, Nishiwaki S, Sugimoto T, Onodera K, Goto T, Sato T, Kamoshita S, Kawashima N, Seto A, Okuno S, Yamamoto S, Iwasaki T, Ozawa Y, Miyamura K, Akatsuka Y, Sugiura I
  • Journal Title: Medicine Volume: 96 Issue: 50 Pages: e9160-e9160
  • DOI: 10.1097/md.0000000000009160
  • Peer Reviewed / Open Access
• [Journal Article] Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study). (2017)
  • Author(s): Nishiwaki S, Sugiura I, Miyata Y, Saito S, Sawa M, Nishida T, Miyamura K, Kuwatsuka Y, Kohno A, Yuge M, Kasai M, Iida H, Kurahashi S, Osaki M, Goto T, Terakura S, Murata M, Nishikawa H, Kiyoi H
  • Journal Title: Medicine Volume: 96 Issue: 52 Pages: e9568-e9568
  • DOI: 10.1097/md.0000000000009568
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Analysis of Combination Chemotherapy Using High Dose Methotrexate, Rituximab, and Vincristine with or without Procarbazine for Elderly Patients with Diffuse Large B-Cell Lymphoma of the Central Nervous System (2017)
  • Author(s): Okamoto S, Tanaka M, Goto T, Nakashima M, Nagura E
  • Journal Title: Gan To Kagaku Ryoho Volume: 44 Pages: 2109-2112
  • Peer Reviewed
• [Journal Article] Prospective observational study on the first 51 cases of peripheral blood stem cell transplantation from unrelated donors in Japan (2017)
  • Author(s): Goto T, Tanaka T, Sawa M, Ueda Y, Ago H, Chiba S, Kanamori H, Nishikawa A, Nougawa M, Ohashi K, Okumura H, Tanimoto M, Fukuda T, Kawashima N, Kato T, Okada K, Nagafuji K, Okamoto SI, Atsuta Y, Hino M, Tanaka J, Miyamura K
  • Journal Title: Int J Hematol. Volume: 107 Issue: 2 Pages: 211-221
  • DOI: 10.1007/s12185-017-2341-y
  • Peer Reviewed
• [Journal Article] High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype (2017)
  • Author(s): Koyama Daisuke、Murata Makoto、Hanajiri Ryo、Okuno Shingo、Kamoshita Sonoko、Julamanee Jakrawadee、Takagi Erina、Hirano Daiki、Miyao Kotaro、Sakemura Reona、Goto Tatsunori、Hayakawa Fumihiko、Seto Aika、Ozawa Yukiyasu、Miyamura Koichi、Terakura Seitaro、Nishida Tetsuya、Kiyoi Hitoshi
  • Journal Title: PLoS One Volume: 12 Issue: 9 Pages: e0185213-e0185213
  • DOI: 10.1371/journal.pone.0185213
  • Peer Reviewed / Open Access
• [Journal Article] Phase II study of intrabone single unit cord blood transplantation for hematological malignancies (2017)
  • Author(s): Murata Makoto、Maeda Yoshinobu、Masuko Masayoshi、et.al
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1634-1639
  • DOI: 10.1111/cas.13291
  • Peer Reviewed / Open Access
• [Journal Article] Impact of T-cell chimerism on relapse after cord blood transplantation for hematological malignancies: Nagoya Blood and Marrow Transplantation Group study (2017)
  • Author(s): Yokohata E, Kuwatsuka Y, Ohashi H, Terakura S, Kawashima N, Seto A, Kurahashi S, Ozawa Y, Goto T, Imahashi N, Nishida T, Miyao K, Sakemura R, Kato T, Sawa M, Kohno A, Sao H, Iida H, Kiyoi H, Naoe T, Miyamura K, Murata M
  • Journal Title: Bone Marrow Transplant. Volume: in press Issue: 4 Pages: 612-614
  • DOI: 10.1038/bmt.2016.323
  • Peer Reviewed
• [Journal Article] Programmed Death-Ligand 1 on Antigen-presenting Cells Facilitates the Induction of Antigen-specific Cytotoxic T Lymphocytes: Application to Adoptive T-Cell Immunotherapy (2016)
  • Author(s): Goto T, Nishida T, Takagi E, Miyao K, Koyama D, Sakemura R, Hanajiri R, Watanabe K, Imahashi N, Terakura S, Murata M, Kiyoi H
  • Journal Title: J Immunother. Volume: 39 Issue: 8 Pages: 306-315
  • DOI: 10.1097/cji.0000000000000136
  • Peer Reviewed
• [Journal Article] A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration (2016)
  • Author(s): Sakemura R, Terakura S, Watanabe K, Julamanee J, Takagi E, Miyao K, Koyama D, Goto T, Hanajiri R, Nishida T, Murata M, Kiyoi H
  • Journal Title: Cancer Immunol Res. Volume: 4 Issue: 8 Pages: 658-668
  • DOI: 10.1158/2326-6066.cir-16-0043
  • Peer Reviewed
• [Presentation] High incidence of extensive chronic gvhd in patients with the REG3A rs7588571 non-GG genotype. (2018)
  • Author(s): Murata M, Koyama D, Hanajiri R, Okuno S, Kamoshita S, Julamanee J, Takagi E, Hirano D, Miyao K, Sakemura R, Goto T, Hayakawa F, Seto A, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H.
  • Organizer: 2018 BMT Tandem Meetings
• [Presentation] Genetically-Modified CD3zeta Improves Proliferation and Persistence of Antigen-specific CTLs (2018)
  • Author(s): 宮尾康太郎、寺倉精太郎、奥野真吾、Jakrawadee Julamanee、渡邉慶介、浜名洋、岸裕幸、酒村玲央奈、小山大輔、後藤辰徳、西田徹也、村田誠、清井仁
  • Organizer: 第40回日本造血細胞移植学会総会
• [Presentation] REG3A遺伝子の一塩基多型rs7588571が非GG型の患者では広範型慢性GVHDの発症頻度が高い (2018)
  • Author(s): 村田誠、小山大輔、葉名尻良、奥野真吾、鴨下園子、Julamanee Jakrawadee、高木えり奈、平野大希、宮尾康太郎、酒村玲央奈、後藤辰徳、早川文彦、瀬戸愛花、小澤幸泰、宮村耕一、寺倉精太郎、西田徹也、清井仁
  • Organizer: 第40回日本造血細胞移植学会総会
• [Presentation] 当院におけるステロイド治療抵抗性急性GVHD に対するヒト間葉系幹細胞治療の後方視的検討 (2017)
  • Author(s): 後藤 辰徳、入山 智沙子、寺倉 精太郎、西田 徹也、村田 誠、清井 仁
  • Organizer: 第39回日本造血細胞移植学会総会
  • Place of Presentation: くにびきメッセ（島根県松江市）
  • Year and Date: 2017-03-02
• [Presentation] 新規人工アダプター分子の遺伝子導入は抗原特異的CTLのpersistenceを向上させる (2017)
  • Author(s): 宮尾康太郎、寺倉精太郎、奥野真吾、渡邊慶介、浜名洋、岸裕幸、酒村玲央奈、Jakrawadee Julamanee、後藤辰徳、西田徹也、村田誠、清井仁
  • Organizer: 第9回血液疾患免疫療法学会学術集会
• [Presentation] ヒト急性GVHDにおける組織浸潤アロ反応性T細胞レパトアの定量的評価 (2017)
  • Author(s): 小山大輔、村田誠、葉名尻良、奥野真吾、鴨下園子、高木えり奈、Jakrawadee Julamanee、宮尾康太郎、後藤辰徳、酒村玲央奈、寺倉精太郎、西田徹也、清井仁
  • Organizer: 第9回血液疾患免疫療法学会学術集会
• [Presentation] ヒト急性GVHDにおける組織浸潤アロ反応性T細胞レパトアの定量的評価 (2017)
  • Author(s): 小山大輔、村田誠、葉名尻良、奥野真吾、鴨下園子、高木えり 奈、Jakrawadee Julamanee、宮尾康 太郎、後藤辰徳、 酒村玲央奈、寺倉精太郎、西田徹也、清井仁
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] Quantitative Assessment of TCR Repertoire and Allo-Reactivity of Human Acute Gvhd Tissue-Infiltrating T Cells (2017)
  • Author(s): Daisuke Koyama, Makoto Murata, Ryo Hanajiri, Shingo Okuno, Sonoko Kamoshita, Erina Takagi, Jakrawadee Julamanee, Kotaro Miyao, Reona Sakemura, Tatsunori Goto, Seitaro Terakura, Tetsuya Nishida and Hitoshi Kiyoi
  • Organizer: 59th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] The Synergistic T-Cell Signal By CD79A/CD40 Costimulatory Endodomain Enhances CD19 Chimeric Antigen Receptor T-Cell Proliferation and Survival (2017)
  • Author(s): Jakrawadee Julamanee, Seitaro Terakura, Reona Sakemura, Kotaro Miyao, Shingo Okuno, Sonoko Kamoshita, Erina Takagi, Daisuke Koyama, Tatsunori Goto, Ryo Hanajiri, Tetsuya Nishida, Makoto Murata and Hitoshi Kiyoi
  • Organizer: 59th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Improvement of antigen-specific CTL persistence by transduction of novel artificial adopter molecule (2016)
  • Author(s): 宮尾 康太郎、寺倉 精太郎、渡邉 慶介、酒村 玲央奈、Jakrawadee Julamanee、奥野 真吾、鴨下 園子、高木 えり奈、小山 大輔、後藤 辰徳、葉名尻 良、西田 徹也、村田 誠、清井 仁
  • Organizer: 58th ASH Annual Meeting and Exposition
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2016-12-03
• [Presentation] REG3A polymorphism is associated with the incidence of extensive chronic GVHD after allogeneic BMT (2016)
  • Author(s): 小山 大輔、村田 誠、葉名尻 良、奥野 真吾、鴨下 園子、Jakrawadee Julamanee、高木 えり奈、宮尾 康太郎、酒村 玲央奈、後藤 辰徳、瀬戸 愛花、小澤 幸泰、宮村 耕一、寺倉 精太郎、西田 徹也、清井 仁
  • Organizer: 58th ASH Annual Meeting and Exposition
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2016-12-03
• [Presentation] Gene modification by adapter molecule improves the expansion of antigen-specific CTL (2016)
  • Author(s): 宮尾 康太郎、寺倉 精太郎、渡邊 慶介、高木 えり奈、Jakrawadee Julamanee, 小山 大輔、酒村 玲央奈、後藤 辰徳、葉名尻 良、西田 徹也、村田 誠、清井 仁
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13
• [Presentation] REG3A polymorphism is associated with the incidence of extensive chronic GVHD after allogeneic BMT (2016)
  • Author(s): 小山 大輔、村田 誠 Jakrawadee Julamanee、高木 えり奈、宮尾 康太郎、酒村 玲央奈、後藤 辰徳、葉名尻 良、瀬戸 愛花、小澤 幸泰、宮村 耕一、寺倉 精太郎、西田 徹也、清井 仁
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-10-13