Development of novel anti-leukemia immunotherapy using neo-antigen specific CD4 helper T cells
| Project/Area Number |
18K08361
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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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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Mie University |
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Principal Investigator |
Fujiwara Hiroshi 三重大学, 医学系研究科, 産学官連携講座准教授 (20398291)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ネオアンチゲン / 遺伝子改変ヘルパーT細胞 / 骨髄性白血病 / 細胞免疫療法 / 白血病幹細胞 / 遺伝子改変T細胞 / 急性骨髄性白血病 / 白血病 / 免疫療法 |
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| Outline of Final Research Achievements |
For the treatment of refractory acute myeloid leukemia (rAML), a currently unmet need, we have been studying the capability of novel adoptive cellular immunotherapy using driver mutation-coded neoantigen reactive T cell receptor (TCR) gene-modified T cells (TCR-T). As a model for driver mutation-coded neoantigen, we chose HTLV-1 p40 Tax, the extrinsic causative factor for adult T-cell leukemia (ATL). We newly achieved HLA-A24 and -A2 restricted TCR αβ genes with high affinities from ATL patients, established TCR gene-modified T cells, and subsequently assessed the capability of this TCR-T therapy. As to development of strategy for neoantigen screening in cancer cells and generation of neoantigen-reactive TCR-T cells using TCR-αβ genes from tumor infiltrating lymphocytes (TIL), instead of rAML, we started to employ cancerous tissues from colon cancer patients, because of its abundance in mutations. Taking above, we are currently expanding this strategy to rAML and other cancers.
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| Academic Significance and Societal Importance of the Research Achievements |
がん細胞特有のネオアンチゲンを認識するT細胞療法は、従来のがん抗原特異的T細胞療法が抱える問題点である正常組織に対するon-target/off-tumor有害事象を解決できる可能性が高い。一方で、がん細胞が持つ遺伝子変異からネオアンチゲンを同定し、かつそれを特異的に認識するTCR遺伝子を腫瘍浸潤Tリンパ球から得て、治療用TCR遺伝子導入T細胞を作製するまでには膨大な作業を要しボトルネックとなっている。この行程を確立出来たことは、今後細胞製剤のみならずがんワクチンの臨床応用の可能性も高める社会的意義がある。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Chromosomal defects and survival in adult T cell leukemia/lymphoma patients after allogeneic HSCT.2021
Author(s)
Nakano N, Utsunomiya A, Matsuo K, Yoshida N, Seto M, Ohshima K, Fujiwara H, Fuji S, Takatsuka1 Y, Ito A, Miyamoto T, Suehiro Y, Nakamae H, Sawayama Y, Yuasa M, Miyazaki Y, Ota S, Imada K, Fukuda T, Ichinohe T, Atsuta Y, Kato K.
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Journal Title
Blood Advances
Volume: 5(2)
Issue: 2
Pages: 475-486
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cytomegalovirus reactivation is associated with increased mortality more than 100 days after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma.2019
Author(s)
Sawayama Y, Itonaga H, Fukushima T, Nakano N, Fujiwara H, Utsunomiya A, Fukuda T, Miyamoto T, Eto T, Miyashita K, Nakamae H, Ogata M, Yamanoha A, Miyazaki Y, Kanda J, Atsuta Y, Kato K; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation.
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Journal Title
American Journal of Hematology
Volume: 94(5)
Issue: 5
Pages: 143-146
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma.2019
Author(s)
Yoshimitsu M, Utsunomiya A, Fuji S, Fujiwara H, Fukuda T, Ogawa H, Takatsuka Y, Ishitsuka K, Yokota A, Okumura H, Ishii K, Nishikawa A, Eto T, Yonezawa A, Miyashita K, Tsukada J, Tanaka J, Atsuta Y, Kato K.
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Journal Title
Bone Marrow Transplant.
Volume: 印刷中
Issue: 8
Pages: 1266-1274
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination.2018
Author(s)
Akahori Y, Wang L, Yoneyama M, Seo N, Okumura S, Miyahara Y, Amaishi Y, Okamoto S, Mineno J, Ikeda H, Maki T, Fujiwara H, Akatsuka Y, Kato T, Shiku H.
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Journal Title
Blood. 2018 Sep 13;132(11):
Volume: 132
Issue: 11
Pages: 1134-1145
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Novel treatment strategy using HTLV-1 p40Tax-specific TCR gene-modified allogeneic gamma/delta-T cells for the treatment of adult T-cell leukemia/lymphoma.2019
Author(s)
Fujiwara H., Okumura S., Fujii K., Miyahara Y, Tawara I., Jo T., Tanaka Y., Tanaka Y., Ikeda H., Shiku H
Organizer
The 10th JSH International Symposium 2019 in Ise-Shima,
Related Report
Int'l Joint Research
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[Presentation] TCR/CAR gene-modified allogeneic gamma/delta-T cells for the treatment of hematological cancers.2019
Author(s)
Fujiwara H., Okumura H., Miwa H., Akahori Y., Miyahara Y., Linan W., Tawara I., Jo T., Tanaka Y., Tanaka Y., Ikeda H., Shiku H.
Organizer
2nd International Conference of Lymphocyte Engineering.
Related Report
Int'l Joint Research
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[Presentation] Novel cellular immunotherapy using allogeneic Vgamma9/delta2-T cells gene-modified to express HTLV-1 P40Tax-specific TCR for the treatment of adult T cell leukemia.2019
Author(s)
Fujiwara H., Okumura S., Fujii K., Miyahara Y., Linan W., Tawara I., Jo T., Tanaka Y., Tanaka Y., Ikeda H., M.D., Shiku H.
Organizer
The 61st American Society of Hematology Annual Meeting and Exposition
Related Report
Int'l Joint Research
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