Enhancement of Intracellular Signaling in T Cell Receptor-transduced T Cells
Project/Area Number |
18K08351
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Nagoya University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 遺伝子導入T細胞療法 / アダプター分子 / Tリンパ球 / TCR遺伝子導入 / T細胞養子免疫療法 / 新規アダプター分子 / 遺伝子導入T細胞 / T細胞内シグナル / 遺伝子改変 |
Outline of Final Research Achievements |
In this study, we attempted to develop a novel vector that enables gene transfer of TCR and adapter molecule (ATAM) into T cells by a single gene transfer. One virus vector method (1vv method) using all-in-one vector and two virus vector (2vv) method using two vectors used in the previous study showed that the expression of ATAM was about 3 times higher in 2vv method. The expression of ATAM was about 3-fold higher in the 2vv method. Comparison of the function of the TCR-T cells generated by the 2vv method showed that the cells generated by the 2vv method proliferated significantly better after antigen stimulation, and the intracellular signals after stimulation showed that the signals of phosphorylated Erk and p38 were significantly enhanced in the TCR-T cells generated by the 2vv method. The results showed that it is necessary to transfer three times more ATAM than TCR.
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Academic Significance and Societal Importance of the Research Achievements |
T細胞レセプター遺伝子と新規に開発したアダプター分子を1回の遺伝子導入によりT細胞内に遺伝子導入可能とする新規ベクターの開発を試みた。ひとつのベクターで遺伝し導入する1 virus vector法(1vv法)と二つのウイルスベクターを用いる方法 (2 virus vector法, 2vv法)を比較したところ、ウェスタンブロット法でも、フローサイト メトリー法でも2vv法でアダプター分子の発現が約3倍程度高く、2vv法で作成したTCR-Tの方が有意に抗原刺激後の増殖が有利であった。TCRよりも3倍以上多くのアダプター分子を遺伝子導入する必要があることが示された。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Comparison of immunosuppressant regimens in salvage cord blood transplantation for graft failure after allogeneic hematopoietic stem cell transplantation2021
Author(s)
Harada K, Fuji S, Seo S, Uchida N, Kawakita T, Yano S, Ozawa Y, Yoshioka S, Onishi Y, Noguchi Y, Onizuka M, Matsuhashi Y, Kimura T, Ichinohe T, Atsuta Y, Terakura S, Nakasone H.
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Journal Title
Bone Marrow Transplant
Volume: 56(2)
Issue: 2
Pages: 400-410
DOI
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Peer Reviewed
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[Journal Article] Phase I clinical trial of intra-bone marrow cotransplantation of mesenchymal stem cells in cord blood transplantation.2021
Author(s)
Goto T, Murata M, Nishida T, Terakura S, Kamoshita S, Ishikawa Y, Ushijima Y, Adachi Y, Suzuki S, Kato K, Hirakawa A, Nishiwaki S, Nishio N, Takahashi Y, Kodera Y, Matsushita T, Kiyoi H.
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Journal Title
Stem Cells Transl Med.
Volume: 10(4)
Issue: 4
Pages: 542-553
DOI
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Peer Reviewed / Open Access
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[Journal Article] A multicenter phase II study of intrabone single-unit cord blood transplantation without antithymocyte globulin.2021
Author(s)
Nishida T, Kobayashi T, Sawa M, Masuda S, Shibasaki Y, Goto T, Fukuhara N, Fujii N, Ikegame K, Sugita J, Ikeda T, Kuwatsuka Y, Suzuki R, Najima Y, Doki N, Kato T, Inagaki Y, Utsu Y, Aotsuka N, Masuko M, Terakura S, Onishi Y, Maeda Y, Okada M, Teshima T, Murata M.
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Journal Title
Annals of Hematology
Volume: 100
Issue: 3
Pages: 743-752
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia2021
Author(s)
Terakura S, Kuwatsuka Y, Sugita J, Takahashi S, Ozawa Y, Ozeki K, Yoshioka S, Nakamae H, Kawakita T, Sawa M, Morishige S, Najima Y, Katsuoka Y, Sakaida E, Kouzai Y, Kimura T, Ichinohe T, Fukuda T, Atsuta Y, Murata M, Teshima T.
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Journal Title
Int J Hematol
Volume: -
Issue: 6
Pages: 840-850
DOI
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Peer Reviewed / Open Access
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[Journal Article] Single Cord Blood Transplantation Versus Unmanipulated Haploidentical Transplantation for Adults with Acute Myeloid Leukemia in Complete Remission.2021
Author(s)
Konuma T, Kanda J, Yamasaki S, Harada K, Shimomura Y, Terakura S, Mizuno S, Uchida N, Tanaka M, Doki N, Ozawa Y, Nakamae H, Sawa M, Matsuoka KI, Morishige S, Maruyama Y, Ikegame K, Kimura T, Kanda Y, Ichinohe T, Atsuta Y, Yanada M.
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Journal Title
Transplant Cell Ther.
Volume: 27(4)
Issue: 4
Pages: 334.e1-334.e11
DOI
Related Report
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[Journal Article] Comparison of Transplantation Outcomes after Foscarnet and Ganciclovir Administration as First-Line Anti-Cytomegalovirus Preemptive Therapy2021
Author(s)
Miyao K, Terakura S, Ozawa Y, Sawa M, Kohno A, Kasahara S, Iida H, Ino K, Kusumoto S, Kasai M, Takami A, Kurahashi S, Kajiguchi T, Morishita T, Nishida T, Murata M; Nagoya Blood and Marrow Transplantation Group.
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Journal Title
Transplant Cell Ther
Volume: 27(4)
Issue: 4
Pages: 342.e1-342.e10
DOI
Related Report
Peer Reviewed
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[Journal Article] Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome2020
Author(s)
Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Goto T, Kohno A, Ozeki K, Onishi Y, Fukuhara N, Fujii N, Yokoyama H, Kasai M, Iida H, Kanemura N, Endo T, Ago H, Onizuka M, Iyama S, Nawa Y, Nakamae M, Nagata Y, Kurahashi S, Tomiya Y, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M
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Journal Title
Bone Marrow Transplantation
Volume: --
Issue: 7
Pages: 1399-1409
DOI
NAID
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Peer Reviewed
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[Journal Article] Updated Comparison of 7/8 HLA Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Umbilical Cord Blood Transplantation as Alternative Donors in Adults with Acute Leukemia.2020
Author(s)
Miyao K, Terakura S, Kimura F, Konuma T, Miyamura K, Yanada M, Kako S, Morhishima S, Uchida N, Toya T, Ozawa Y, Fukuda T, Tanaka M, Sawa M, Takada S, Yoshida S, Kimura T, Ichinohe T, Atsuta Y, Kanda J
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Journal Title
Biol Blood Marrow Transplant.
Volume: 26(11)
Issue: 11
Pages: 2105-2114
DOI
Related Report
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[Journal Article] Artificial T cell adaptor molecule-transduced TCR-T cells demonstrated improved proliferation only when transduced in a higher intensity.2020
Author(s)
Sakai T, Terakura S, Miyao K, Okuno S, Adachi Y, Umemura K, Julamanee J, Watanabe K, Hamana H, Kishi H, Leitner J, Steinberger P, Nishida T, Murata M, Kiyoi H.
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Journal Title
Mol. Ther. Oncolytics
Volume: 18
Pages: 613-622
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol.2020
Author(s)
Terakura S, Konuma T, Tanaka M, Ozawa Y, Onizuka M, Nanno S, Onishi Y, Aotsuka N, Kondo T, Kawakita T, Kato J, Kobayashi T, Nishida T, Yamaguchi T, Kuwatsuka Y, Takahashi S.
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Journal Title
BMJ Open.
Volume: 10(12)
Issue: 12
Pages: e040467-e040467
DOI
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Peer Reviewed / Open Access
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[Journal Article] Effect of cytomegalovirus reactivation with or without acute graft-versus-host disease on the risk of nonrelapse mortality2020
Author(s)
Akahoshi Y, Kimura SI, Inamoto Y, Seo S, Muranushi H, Shimizu H, Ozawa Y, Tanaka M, Uchida N, Kanda Y, Katayama Y, Shiratori S, Ota S, Matsuoka KI, Onizuka M, Fukuda T, Atsuta Y, Murata M, Terakura S, Nakasone H.
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Journal Title
Clin Infect Dis
Volume: -
Issue: 3
Pages: e620-e628
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[Journal Article] Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation.2020
Author(s)
Kamoshita S, Murata M, Koyama D, Julamanee J, Okuno S, Takagi E, Miyao K, Goto T, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H.
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Journal Title
International Journal of Hematology
Volume: 111
Issue: 1
Pages: 112-119
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome2020
Author(s)
Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Kohno A, Onishi Y, Fukuhara N, Kasai M, Fujii N, Yokoyama H, Iida H, Kanemura N, Fujieda A, Ago H, Tsutsumi Y, Nakamura F, Yago K, Moriuchi Y, Ota S, Ohashi H, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M
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Journal Title
Biology of Blood and Marrow Transplantation
Volume: 26
Issue: 1
Pages: 139-144
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[Journal Article] Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning2020
Author(s)
Terakura S, Onizuka M, Fukumoto M, Kuwatsuka Y, Kohno A, Ozawa Y, Miyamura K, Inagaki Y, Sawa M, Atsuta Y, Suzuki R, Naoe T, Morishita Y, Murata M
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Journal Title
Int J Hematol
Volume: 111
Issue: 1
Pages: 84-92
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[Journal Article] Quantitative Assessment of T Cell Clonotypes in Human Acute Graft-versus-Host Disease Tissues.2019
Author(s)
Koyama D, Murata M, Hanajiri R, Akashi T, Okuno S, Kamoshita S, Julamanee J, Takagi E, Miyao K, Sakemura R, Goto T, Terakura S, Nishida T, Kiyoi H
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Journal Title
Biol Blood Marrow Transplant
Volume: 25
Issue: 3
Pages: 417-423
DOI
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Peer Reviewed / Open Access
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[Journal Article] Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors.2019
Author(s)
Wakamatsu M, Terakura S, Ohashi K, Fukuda T, Ozawa Y, Kanamori H, Sawa M, Uchida N, Ota S, Matsushita A, Kanda Y, Nakamae H, Ichinohe T, Kato K, Murata M, Atsuta Y, Teshima T.
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Journal Title
Blood Adv
Volume: 3
Issue: 2
Pages: 105-115
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[Journal Article] Introduction of genetically modified CD3ζ improves proliferation and persistence of antigen-specific CTLs.2018
Author(s)
Miyao K, Terakura S, Okuno S, Julamanee J, Watanabe K, Hamana H, Kishi H, Sakemura R, Koyama D, Goto T, Nishida T, Murata M, Kiyoi H.
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Journal Title
Cancer Immunol Res
Volume: 6
Issue: 6
Pages: 733-744
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[Journal Article] Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol2018
Author(s)
Goto T, Murata M, Terakura S, Nishida T, Adachi Y, Ushijima Y, Shimada K, Ishikawa Y, Hayakawa F, Nishio N, Nishiwaki S, Hirakawa A, Kato K, Takahashi Y, Kiyoi H
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Journal Title
Medicine
Volume: 97
Issue: 17
Pages: e0449-e0449
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[Journal Article] Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia.2018
Author(s)
Hattori H, Ishikawa Y, Kawashima N, Akashi A, Yamaguchi Y, Harada Y, Hirano D, Adachi Y, Miyao K, Ushijima Y, Terakura S, Nishida T, Matsushita T, Kiyoi H
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Journal Title
PLoS One
Volume: 13
Issue: 10
Pages: e0204850-e0204850
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[Presentation] 成人難治性血液悪性腫瘍に対する非血縁者間臍帯血移植の有効性に関する研究(臨床第II相試験)2020
Author(s)
澤 正史, 寺倉精太郎, 西田徹也, 加藤智則, 宮尾康太郎, 小澤幸泰, 河野彰夫, 大西 康, 福原規子, 笠井雅信, 藤井伸治, 横山寿行, 飯田浩充, 兼村信宏, 藤枝敦史, 吾郷浩厚, 堤 豊, 中村文彦, 野吾和宏, 森内幸美, 太田秀一, 大橋春彦, 柳澤昌実, 鈴木律朗, 鍬塚八千代, 熱田由子, 宮村耕一, 村田 誠.
Organizer
第42回日本造血細胞移植学会総会
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[Presentation] Phase I Study of Cord Blood Transplantation with Intra-Bone Marrow Injection of Mesenchymal Stem Cells.2019
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Goto T, Murata M, Nishida T, Terakura S, Kamoshita S, Ishikawa Y, Ushijima Y, Adachi Y, Kato K, Hirakawa A, Nishiwaki S, Nishio N, Takahashi Y, Kodera Y, Matsushita T, Kiyoi H.
Organizer
The 61th Annual Meeting of the American Society of Hematology
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[Presentation] Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood.2019
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Terakura S, Nishida T, Sawa M, Kato T, Miyao K, Ozawa Y, Goto T, Kohno A, Ozeki K, Onishi Y, Fukuhara N, Fujii N, Yokoyama H, Kasai M, Iida H, Kanemura N, Endo T, Ago H, Onizuka M, Iyama S, Nawa Y, Nakamae M, Nagata Y, Kurahashi S, Tomiya Y, Yanagisawa A, Suzuki R, Kuwatsuka Y, Atsuta Y, Miyamura K, Murata M.
Organizer
The 61th Annual Meeting of the American Society of Hematology
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[Presentation] Impacts of ATG for conditioning in patients with acute leukemia undergoing allogeneic HSCT across different donors2019
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日本造血細胞移植学会
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