A novel pathway regulating memory T cell development for cancer immunotherapy

• Project/Area Number: 26430162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: Fujiki Fumihiro 大阪大学, 医学系研究科, 特任助教(常勤) (40456926)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: メモリーT細胞 / 腫瘍免疫 / 癌免疫療法

Outline of Final Research Achievements

Efficient memory T cell induction has been demanded for the development of a potent cancer immunotherapy. However, it remains unclear how memory T cell is induced. We previously identified a novel nutrient metabolism regulating the differentiation of memory T cell. Here, we show that new inhibitors against the metabolism process can enhance the efficacy of T cell-based cancer immunotherapy. Furthermore, we also demonstrate a novel mechanism regulating the expression of L-Selectin (CD62L), an important functional marker for memory T cells, in T cells. Thus, these results should provide us with a methodology for controlling T cell differentiation and contribute to develop more effective cancer immunotherapy.

Research Products

• [Journal Article] Syndecan-4 as a biomarker to predict clinical outcome for glioblastoma multiforme treated with WT1 peptide vaccine (2016)
  • Author(s): Takashima S, Oka Y, Fujiki F, Morimoto S, Nakajima H, Nakae Y, Nakata J, Nishida S, Hosen N, Tatsumi N, Mizuguchi K, Hashimoto N, Oji Y, Tsuboi A, Kumanogoh A, Sugiyama H
  • Journal Title: Future Sci OA Volume: FSO96 Issue: 4
  • DOI: 10.4155/fsoa-2015-0008
  • Peer Reviewed / Open Access
• [Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. (2016)
  • Author(s): Oji Y, Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Elisseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
  • Journal Title: Int J Cancer. Volume: 139 Issue: 6 Pages: 1391-401
  • DOI: 10.1002/ijc.30182
  • Peer Reviewed / Open Access
• [Journal Article] Glycosylation Status of CD43 Protein Is Associated with Resistance of Leukemia Cells to CTL-Mediated Cytolysis. (2016)
  • Author(s): Hasegawa K, Tanaka S, Fujiki F, Morimoto S, Nakano K, Kinoshita H, Okumura A, Fujioka Y, Urakawa R, Nakajima H, Tatsumi N, Nakata J, Takashima S, Nishida S, Tsuboi A, Oka Y, Oji Y, Miyoshi E, Hirata T, Kumanogoh A, Sugiyama H, Hosen N.
  • Journal Title: PLoS One Volume: 11 Issue: 3 Pages: e0152326-e0152326
  • DOI: 10.1371/journal.pone.0152326
  • Peer Reviewed / Open Access
• [Journal Article] An essential role of the avidity of T-cell receptor in differentiation of self-antigen-reactive CD8+ T cells (2016)
  • Author(s): Kondo K, Fujiki F, Nakajima H, Yatsukawa E, Morimoto S, Tatsumi N, Nishida S, Nakata J, Oka Y, Tsuboi A, Hosen N, Oji Y, Sugiyama H
  • Journal Title: Journal of Immunotherapy Volume: 39 Issue: 3 Pages: 127-139
  • DOI: 10.1097/cji.0000000000000114
  • Peer Reviewed / Open Access
• [Journal Article] A Zbtb7a proto-oncogene as a novel target for miR-125a. (2016)
  • Author(s): Hojo N, Tatsumi N, Moriguchi N, Matsumura A, Morimoto S, Nakata J, Fujiki F, Nishida S, Nakajima H, Tsuboi A, Oka Y, Hosen N, Hayashi S, Sugiyama H, Oji Y.
  • Journal Title: Molecular Carcinogenesis Volume: - Issue: 12 Pages: 1-9
  • DOI: 10.1002/mc.22446
  • Peer Reviewed / Open Access
• [Journal Article] An Immunocompetent Mouse Model for MLL/AF9 Leukemia Reveals the Potential of Spontaneous Cytotoxic T-Cell Response to an Antigen Expressed in Leukemia Cells. (2015)
  • Author(s): Hasegawa K, Tanaka S, Fujiki F, Morimoto S, Nakajima H, Tatsumi N, Nakata J, Takashima S, Nishida S, Tsuboi A, Oka Y, Oji Y, Kumanogoh A, Sugiyama H, Hosen N.
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed
• [Journal Article] Two distinct effector memory cell populations of WT1 (Wilms' tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients (2015)
  • Author(s): Nakae Y., Oka Y., Fujiki F., Morimoto S., Kamiya T., Takashima S., Nakata J., Nishida S., Nakajima H., Hosen N., Tsuboi A, Kyo T., Oji Y., Mizuguchi K., Kumanogoh A., Sugiyama H.
  • Journal Title: Cancer Immunology, Immunotherapy Volume: in press Issue: 7 Pages: 791-804
  • DOI: 10.1007/s00262-015-1683-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transduction of a Novel HLA-DRB1*04:05-restricted, WT1-specific TCR Gene into Human CD4+ T Cells Confers Killing Activity Against Human Leukemia Cells. (2015)
  • Author(s): Katsuhara A, Fujiki F, Aoyama N, Tanii S, Morimoto S, Oka Y, Tsuboi A, Nakajima H, Kondo K, Tatsumi N, Nakata J, Nakae Y, Takashima S, Nishida S, Hosen N, Sogo S, Oji Y, Sugiyama H.
  • Journal Title: Anticancer Research Volume: 35 Pages: 1251-1261
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Electroporation of Dicer-Substrate siRNA Duplexes Targeting Endogenous TCR Enhance Tumor Killing Activity of Wilms' Tumor 1 (WT1)-Specific TCR-Redirected Cytotoxic T Cells (2016)
  • Author(s): Diana Campillo-Davo, Fumihiro Fujiki, Johan M.J. Van den Bergh, Evelien L. Smits, Haruo Sugiyama, Viggo F.I. Van Tendeloo and Zwi N. Berneman
  • Organizer: ASH Annual Meeting
  • Place of Presentation: San Diego Convention Center
  • Int'l Joint Research
• [Presentation] Cloning of WT1332 helper peptide-specific TCRs and their application for cancer immunotherapy (2015)
  • Author(s): Fumihiro Fujiki, Akiko Katsuhara, Yuhung Lin, Nao Aoyama, Satoe Tanii, Soyoko Morimoto, Hiroko Nakajima, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama
  • Organizer: The 8th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: KBS Kyoto Hall, Kyoto, JAPAN
  • Year and Date: 2015-11-19
• [Presentation] Isolation and validation of WT1-specific T cell receptors from leukemia patients after successful DC vaccination for redirected T-cell immunotherapy (2015)
  • Author(s): Fumihiro Fujiki, Diana Campillo-Davo, Johan Van den Bergh, Evelien Smits, Zwi Berneman, Haruo Sugiyama, Viggo Van Tendeloo
  • Organizer: The 8th International Conference on WT1 in Human Neoplasia
  • Place of Presentation: KBS Kyoto Hall, Kyoto, JAPAN
  • Year and Date: 2015-11-19
• [Presentation] HLA クラス II 拘束性 WT1 由来ヘルパーペプチド特異的 TCR 遺伝子を導入され た CD4+ T 細胞は in vivo において anti-leukemia activity を発揮する (2014)
  • Author(s): 勝原晶子、藤木文博、青山奈央 、谷井里江、森本創世子、岡芳弘、坪井昭博、中島博子、辰巳直也、保仙直毅、尾路祐介、杉山治夫
  • Organizer: 第6回血液疾患免疫療法研究会
  • Place of Presentation: 京都大学 芝蘭会館
  • Year and Date: 2014-09-06
• [Presentation] Analysis of correlation of WT1-specific immune responses before WT1 peptide vaccination and clinical responses (2014)
  • Author(s): Soyoko Morimoto, Yoshihiro Oka, Akihiro Tsuboi, Naoki Hosen, Sumiyuki Nishida, Fumihiro Fujiki, Hiroko Nakajima, Yusuke Oji, Haruo Sugiyama
  • Organizer: The 7th International Conference on WT1 in human neoplasia
  • Place of Presentation: Hospital Sant Pau, Events Hall, Barcelona
  • Year and Date: 2014-04-22 – 2014-04-23