Therapeutic employment of leukemia-reactive CD4-CD8 T-cell network aiming at improved clinical efficacy.
| Project/Area Number |
15K09506
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 遺伝子細胞免疫療法 / 遺伝子改変T細胞 / T細胞受容体遺伝子 / キメラ型抗原受容体遺伝子 / 白血病幹細胞 / 抗腫瘍性T細胞ネットワーク / 免疫記憶細胞 / 養子免疫療法 / T細胞受容体（TCR）遺伝子 / キメラ型抗原受容体（CAR）遺伝子 / 細胞免疫療法 / キメラ型受容体（CAR）遺伝子 |
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| Outline of Final Research Achievements |
Aiming at a clinically effective gene-modified T-cell based adoptive immunotherapy against human leukemias, we multilaterally studied the leukemia reactive T-cell network comprising leukemia stem cell reactive T-cell receptor (TCR) gene modified CD8 killer T cells and CD4 helper T cells, targeting Wilms Tumor 1 (WT1) and Aurora Kinase A (AURKA).This study included a unique HLA class I restricted TCR gene-modified CD4 T cells and autologous transplantation using WT1-specific TCR gene-modified hematopoietic stem cells. In parallel, we conducted a clinical trial.
Additionally, we also have developed a novel chimeric antigen receptor (CAR) gene-modified T cells, expressing affinity-increased CD16 which can employ anticancer monoclonal antibodies for target recognition, e.g., mogamulizumab against adult T cell leukemia. Furthermore, we are now developing a novel CAR gene which can recognize an epitope/HLA complex derived from cytoplasmic cancer antigens like as TCR-T cells.
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Report
(4 results)
Research Products
(84 results)
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[Journal Article] Safety and persistence of WT1-specific T-cell receptor gene-transduced lymphocytes in patients with AML and MDS.2017
Author(s)
Tawara I, Kageyama S, Miyahara Y, Fujiwara H, Nishida T, Akatsuka Y, Ikeda H, Tanimoto K, Terakura S, Murata M, Inaguma Y, Masuya M, Inoue N, Kidokoro T, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Naoe T, Emi N, Yasukawa M, Katayama N, Shiku H.
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Journal Title
Blood
Volume: 130
Issue: 18
Pages: 1985-1994
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dismal outcome of allogeneic hematopoietic stem cell transplantation for relapsed adult T-cell leukemia/lymphoma, a Japanese nation-wide study.2017
Author(s)
Fujiwara H, Fuji S, Wake A, Kato K, Takatsuka Y, Fukuda T, Taguchi J, Uchida N, Miyamoto T, Hidaka M, Miyazaki Y, Tomoyose T, Onizuka M, Takanashi M, Ichinohe T, Atsuta Y, Utsunomiya A; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation.
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Journal Title
Bone Marrow Transplantation
Volume: 52 (3)
Issue: 3
Pages: 484-488
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] T-cell Receptor Signaling Activates an ITK/NF-κB/GATA-3 axis in T-cell Lymphomas Facilitating Resistance to Chemotherapy.2017
Author(s)
Wang T, Lu Y, Polk A, Chowdhury P, Zamalloa CM, Fujiwara H, Suemori K, Beyersdorf N, Hristov AC, Lim MS, Bailey NG, Wilcox RA.
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Journal Title
Clinical Cancer Research
Volume: in print
Issue: 10
Pages: 2506-2515
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia-Lymphoma: ATLL-002.2016
Author(s)
Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T.
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Journal Title
J Clin Oncol.
Volume: ３４
Issue: 34
Pages: 4086-4093
DOI
Related Report
Peer Reviewed
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[Journal Article] Induction of WT1-specific human CD8+ T cells from human HSCs in HLA class I Tg NOD/SCID/IL2rgKO mice.2016
Author(s)
Najima Y, Tomizawa-Murasawa M, Saito Y, Watanabe T, Ono R, Ochi T, Suzuki N, Fujiwara H, Ohara O, Shultz LD, Yasukawa M, Ishikawa F.
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Journal Title
Blood
Volume: 127(6)
Issue: 6
Pages: 722-734
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Early application of related SCT might improve clinical outcome in adult T-cell leukemia/lymphoma.2016
Author(s)
Fuji S, Fujiwara H, Nakano N, Wake A, Inoue Y, Fukuda T, Hidaka M, Moriuchi Y, Miyamoto T, Uike N, Taguchi J, Eto T, Tomoyose T, Kondo T, Yamanoha A, Ichinohe T, Atsuta Y, Utsunomiya A; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation.
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Journal Title
Bone Marrow Transplantation
Volume: 51(2)
Issue: 2
Pages: 205-211
DOI
Related Report
Peer Reviewed
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[Journal Article] Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.2015
Author(s)
Fujiwara H, Ochi T, Ochi F, Miyazaki Y, Asai H, Narita M, Okamoto S, Mineno J, Kuzushima K, Shiku H, Yasukawa M.
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Journal Title
Leukemia
Volume: 29(12)
Issue: 12
Pages: 2393-2401
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study.2015
Author(s)
Ishida T, Jo T, Takemoto S, Suzushima H, Uozumi K, Yamamoto K, Uike N, Saburi Y, Nosaka K, Utsunomiya A, Tobinai K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Moriuchi Y, Imada K, Miyamoto T, Akinaga S, Tomonaga M, Ueda R
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Journal Title
Br J Haematol
Volume: 未定
Issue: 5
Pages: 672-682
DOI
Related Report
Peer Reviewed
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[Presentation] Development of T-cell therapy by exploiting modified antibodies specific for A2/NY-ESO-1 for refractory myeloma.2017
Author(s)
Maruta, M., Ochi, T., Tanimoto, K., Azuma, T., Fujiwara, H., Yasukawa, M.
Organizer
The 59th American Society of Hematology Annual Meeting and Exposition
Related Report
Int'l Joint Research
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[Presentation] Development of immunotherapy for myeloma utilizing T cells redirected with modified antibodies specific for NY-ESO-1.2017
Author(s)
Ochi, T., Maruta, M., Tanimoto, K., Azuma, T., Fujiwara, H., Yasukawa M.
Organizer
The 36th Sapporo International Cancer Symposium
Related Report
Int'l Joint Research
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[Presentation] Adoptive immunotherapy using WT1-specific T-cell receptor gene-modified lymphocytes for the treatment of patients with acute myelogenous leukemia and myelodysplastic syndrome.2016
Author(s)
Fujiwara H, Tanimoto K, Tawara I, Masuya M, Miyahara Y, Nishida T, Murata M, Terakura S, Akatsuka Y, Ikeda H, Kageyama S, Nukaya I, Takesako K, Nobuyuki Emi N, Katayama N, Shiku H, Yasukawa M.
Organizer
The 7th JSH International Symposium
Place of Presentation
Awaji, Hyogo, Japan, Westin Hotel Awaji
Year and Date
2016-05-24
Related Report
Int'l Joint Research / Invited
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[Presentation] Wilms Tumor 1 specific T-cell receptor gene-modified autologous lymphocytes displayed a transient clinical response in a patient with acute myeloid leukemia.2016
Author(s)
Hiroshi Fujiwara, Kazushi Tanimoto, Nicholas Casey, Taichi Azuma, Kazuto Takeuchi, Shinichi Kageyama, Hiroaki Ikeda, Sachiko Okamoto, Junichi Mineno, Hiroyoshi Nishikawa, Hiroshi Shiku, Masaki Yasukawa
Organizer
42nd Annual Meeting of the European Society for Blood and Marrow Transplantation
Place of Presentation
Valencia, Spain
Year and Date
2016-04-06
Related Report
Int'l Joint Research
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[Presentation] Immunotherapy with Chimeric Antigen Receptor Targeting Intracellular WT1 Gene Product Complexed with HLA-A*24:02 Molecule2015
Author(s)
Hiroaki Ikeda, Yasushi Akahori, Motohiro Yoneyama, Yuki Orito, Yoshihiro Miyahara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Kazutoh Takesako, Hiroshi Fujiwara, Masaki Yasukawa, Hiroshi Shiku
Organizer
57th Annual Meeting of American Society of Hematology
Place of Presentation
Orlando, FL, USA
Year and Date
2015-12-07
Related Report
Int'l Joint Research
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[Presentation] Multicenter Phase II Study of Lenalidomide in Patients with Relapsed Adult T-Cell Leukemia-Lymphoma2015
Author(s)
Hiroshi Fujiwara, Takashi Ishida, Kisato Nosaka, Naoya Taira, Yasunobu Abe, Yoshitaka Imaizumi, Yukiyoshi Moriuchi, Tatsuro Jo, Kenichi Ishizawa, Kensei Tobinai, Kunihiro Tsukasaki, Shigeki Ito, Makoto Yoshimitsu, Maki Otsuka, Michinori Ogura, Shuichi Midorikawa, Wanda Ruiz, Tomoko Ohtsu
Organizer
57th Annual Meeting of American Society of Hematology
Place of Presentation
Orlando, FL, USA
Year and Date
2015-12-06
Related Report
Int'l Joint Research
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[Presentation] Adoptive Transfer of WT1-Specific TCR Gene-Transduced Lymphocytes in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia2015
Author(s)
Isao Tawara, Masahiro Masuya, Shinichi Kageyama, Tetsuya Nishida, Seitaro Terakura, Makoto Murata, Hiroshi Fujiwara, Yoshiki Akatsuka, Hiroaki Ikeda, Yoshihiro Miyahara, Daisuke Tomura, Ikuei Nukaya, Kazutoh Takesako, Nobuhiko Emi, Masaki Yasukawa, Naoyuki Katayama, Hiroshi Shiku
Organizer
57th Annual Meeting of American Society of Hematology
Place of Presentation
Orlando, FL, USA
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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[Presentation] A phase I clinical trial of adoptive transfer of WT1 redirected T cells for refractory AML and MDS2015
Author(s)
Hiroshi Fujiwara, Isao Tawara, Kazushi Tanimoto, Tetsuya Nishida, Makoto Murata, Seitaro Terakura, Ikuei Nukaya, Yoshiki Akatsuka, Masataka Okamoto, Masahiro Masuya, Hiroaki Ikeda, Sinichi Kageyama, Nobuhiko Emi, Naoyuki Katayama, Masaki Yasukawa, Hiroshi Shiku
Organizer
第77回 日本血液学会学術集会
Place of Presentation
石川県金沢市 ホテル日航金沢
Year and Date
2015-10-17
Related Report
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