Identification of factors that determine the fate of functional T cells in vivo and development of effective TCR gene-modified T cell therapy
Project/Area Number |
24390300
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
General surgery
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Research Institution | Mie University |
Principal Investigator |
IKEDA Hiroaki 三重大学, 医学(系)研究科(研究院), 教授 (40374673)
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Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2012: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
|
Keywords | T細胞 / マルチファンクション性 / T細胞輸注療法 / 遺伝子治療 / 癌 / 免疫記憶 / T細胞受容体 / キメラ抗原受容体 / 生存性 |
Outline of Final Research Achievements |
We found that CD28 stimuli induced short-lived but highly cytotoxic T cells whereas VLA-4/5 stimuli induced T cells with memory formation potential and high multifuctionality upon recall. We performed a phase I clinical trial with T cells with genetically engineered to express MAGE-A4-specific TCR for esophageal cancer patients. In this trial, we found that the long-term existence of the infused cells did not correlate with the clinical response when the patients did not receive lympho-depletive pre-treatment. Utilizing an original retroviral vector that inhibits the expression of endogenous TCR, we demonstrated a model of adoptive therapy with allogeneic T cells that induce less GvHD and increased tumor reactivity. We generated an antibody that reacted to the complex of HLA and a peptide from intracellular antigen and showed the usefulness of a chimeric antigen receptor that utilize this antibody.
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Report
(4 results)
Research Products
(49 results)
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[Journal Article] Stimulation through very late antigen-4 and -5 improves the multifunctionality and memory formation of CD8+ T cells.2014
Author(s)
Hosoi H, Ikeda H, Imai N, Amaike C, Wang L, Orito Y, Yamane M, Ueno H, Ideno M, Nukaya I, Enoki T, Mineno J, Takesako K, Hirano S, Shiku H.
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Journal Title
European Journal of Immunology
Volume: 44
Issue: 6
Pages: 1727-1758
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Adoptive transfer of genetically engineered WT1-specific cytotoxic T lymphocytes does not induce renal injury2014
Author(s)
Asai H, Fujiwara H, Kitazawa S, Kobayashi N, Ochi T, Miyazaki Y, Ochi F, Akatsuka Y, Okamoto S, Mineno J, Kuzushima K, Ikeda H, Shiku H, Yasukawa M
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Journal Title
J Hematol Oncol.
Volume: 7
Issue: 1
Pages: 3-3
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients2013
Author(s)
Kageyama S, Wada H, Muro K, Niwa Y, Ueda S, Miyata H, Takiguchi S, Sugino SH, Miyahara Y, Ikeda H, Imai N, Sato E, Yamada T, Osako M, Ohnishi M, Harada N, Hishida T, Doki Y, Shiku H
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Journal Title
Journal of translational medicine
Volume: 5;11
Issue: 1
Pages: 246-246
DOI
Related Report
Peer Reviewed
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[Journal Article] Adoptive transfer of genetically modified Wilms' tumor 1-specific T cells in a novel malignant skull base meningioma model.2013
Author(s)
Iwami K, Natsume A, Ohno M, Ikeda H, Mineno J, Nukaya I, Okamoto S, Fujiwara H, Yasukawa M, Shiku H, Wakabayashi T.
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Journal Title
Neuro Oncol.
Volume: 15
Issue: 6
Pages: 747-758
DOI
Related Report
Peer Reviewed
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[Journal Article] Limited expression of cancer-testis antigen in renal eell carcinoma patients.2013
Author(s)
Soga N, Hori Y, Yamakado K, Ikeda H, Imai N, Kageyama S, Nakase K, Yuta A, Hayashi N, Shiku H, S
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Journal Title
Mol. Clin. Oncol.
Volume: 1
Issue: 2
Pages: 326-330
DOI
Related Report
Peer Reviewed
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[Journal Article] Intracellular Tumor-Associated Antigens Represent Effective Targets for Passive Immunotherapy2012
Author(s)
Noguchi, T., T.Kato, L.Wang, Y.Maeda, H.Ikeda, E.Sato, A.Knuth, S.Gnjatic, G.Ritter, S.Sakaguchi, L.J.Old, H.Shiku, H.Nishikawa
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Journal Title
Cancer Research
Volume: 72
Issue: 7
Pages: 1672-1682
DOI
Related Report
Peer Reviewed
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[Presentation] Tumor-specific TCR-engineered donor lymphocyte infusion therapy with reduced GVHD induction utilizing novel retrovirus vector silencing endogenous TCR expression.2014
Author(s)
Hiroaki Ikeda, Hiroaki Ueno, Isao Tawara, Ayumi Kawamura, Naoko Imai, Sachiko Okamoto, Junichi Mineno, Kazutoh Takesako, Naoyuki Katayama, Hiroshi Shiku.
Organizer
American Society of Hematology 56th annual meeting
Place of Presentation
San Francisco, USA
Year and Date
2014-12-08
Related Report
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[Presentation] TCR gene therapy with allogeneic T cells2014
Author(s)
Hiroaki Ikeda, Hiroaki Uneno, Ayumi Kawamura, Makiko Yamane, Naoko Imai, Sachiko Okamoto, Junichi Mineno, Kazutoh Takesako, Hiroshi Shiku.
Organizer
第20回日本遺伝子治療学会学術集会
Place of Presentation
東京慈恵会医科大学、東京
Year and Date
2014-08-08
Related Report
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[Presentation] ANTIGEN RECEPTOR GENE-MODIFIED LYMPHOCYTES : HARNESSING T CELLS FOR EFFECTIVE CANCER TREATMENT WITH NOVEL VECTORS AND MANIPULATIONS2013
Author(s)
Ikeda H, Kageyama S, Imai N, Miyahara Y, Ishihara M, Kawamura A, Yamane M, Tomura D, Okamoto S, Nukaya I, Mineno J, Takesako K Katayama N, Shiku H.
Organizer
Ninth AACR-Japanese Cancer Association Joint Conference
Place of Presentation
Maui, HI, USA
Year and Date
2013-02-24
Related Report
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[Presentation] Adoptively transferred TCR gene-transduced lymphocytes persist with anti-tumor reactivity in patients with MAGE-A4+ esophageal cancer2013
Author(s)
Hiroaki Ikeda, Shinichi Kageyama, Naoko Imai, Yoshihiro Miyahara, Mikiya Ishihara, Yasuhiro Nagata, Naoyuki Katayama, Hirofumi Yoshioka, Daisuke Tomura, Ikuei Nukaya, Junichi Mineno, Kazuto Takesako, Hiroshi Shiku
Organizer
ESGCT and SETGyC Collaborative Congress, Madrid
Place of Presentation
Madrid, Spain
Related Report
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[Presentation] In vivo persistence of adoptively transferred TCR gene-transduced lymphocytes with anti-tumor reactivity in patients with MAGE-A4 expressing esophageal cancer2013
Author(s)
Hiroaki Ikeda, Shinichi Kageyama, Naoko Imai, Yoshihiro Miyahara, Mikiya Ishihara, Naoyuki Katayama, Hirofumi Yoshioka, Daisuke Tomura, Ikuei Nukaya, Junichi Mineno, Kazuto Takesako, Hiroshi Shiku
Organizer
28th Annual Meeting of Society for Immunotherapy of Cancer
Place of Presentation
National Harbor, MD, USA
Related Report
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[Presentation] Evaluation of vector construction of TCR gene therapy for cancer utilizing a novel mouse model.2012
Author(s)
Imai N, Kawamura A, Yamane M, Wang L, Shirakura K, Shi rakura K, Amaike C, Goto Y, Okamoto S, Mineno J, Takesako K Ikeda H, Shiku H.
Organizer
第41回日本免疫学会学術集会
Place of Presentation
神戸
Year and Date
2012-12-06
Related Report
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[Presentation] In vivo persistence of adoptively transferred TCR gene-transduced lymphocytes in patients wi th esophageal cancer.2012
Author(s)
Kageyama S, Iked a H, Miyahara Y, Imai N, Ishihara M, Saito K, Katayama N, Ueda S, Tomura D, Nukaya I, Mineno J, Takesako K, Shiku H.
Organizer
第71回日本癌学会学術総会
Place of Presentation
札幌
Year and Date
2012-09-19
Related Report
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[Presentation] Clinical application of gene-modified lymphocytes for cancer immunotherapy.2012
Author(s)
Ikeda H, Kageyama S, Imai N, Miyahara Y, Ishihara M, Kawamura A, Yamane M, Tomura D, Okamoto S, Nukaya I, Mineno J, Takesako K, Katayama N, Shiku H.
Organizer
第18回日本遺伝子治療学会学術集会
Place of Presentation
熊本(招待講演)
Year and Date
2012-06-29
Related Report
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[Presentation] Evaluation of "siTCR" vectors using novel mouse model of T cell receptor gene therapy.2012
Author(s)
Imai N, Kawamura A Yamane M, Wang L, Shirakura K, Shirakura K, Amaike C, Goto Y, Okamoto S, Mineno J, Takesako K Ikeda H, Shiku H.
Organizer
第18回日本遺伝子治療学会学術集会
Place of Presentation
熊本
Year and Date
2012-06-29
Related Report
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