Identification of key genes that is correlated with long-term maintenance of cytotoxic activity in WT1 specific cytotoxic T lymphocytes

• Project/Area Number: 25830116
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Osaka University
• Principal Investigator: MORIMOTO Soyoko 大阪大学, 医学(系)研究科(研究院), 研究員 (10649023)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: WT1特異的CTL / single cell定量PCR / WT1 / memory

Outline of Final Research Achievements

High frequency of WT1 specific effector-memory CTL involved in the appearance of good clinical response. However key genes specifying such effector-memory CTL were unknown. To find out genes specifying function of WT1 specific CTL which has cytotoxic activity for a long time, we established a method of multiple gene-expression analysis using single-cell real-time PCR. This analysis revealed that WT1 specific effector-memory CTL population from cancer patients could be divided into two groups: the “activated” and “quiescent” states. These results suggest that this unique gene expression in WT1 specific effector-memory T cell contributed to meaningful function of CTL for induction of good clinical response.

Research Products

• [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): Akiko Katsuhara, Fumihiro Fujiki, Nao Aoyama, Satoe Tanii, Soyoko Morimoto, Yoshihiro Oka, Akihiro Tsuboi, Hiroko Nakajima, Kenta Kondo, Naoya Tatsumi, Jun Nakata, Yoshiki Nakae, Satoshi Takashima, Sumiyuki Nishida, Naoki Hosen, Shinji Sogo, Yusuke Oji, Haruo Sugiyama
  • Journal Title: Anticancer Research Volume: 35 Pages: 1251-1262
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response (2015)
  • Author(s): Naoya Hashimoto, Akihiro Tsuboi, Naoki Kagawa, Yasuyoshi Chiba, Shuichi Izumoto, Manabu Kinoshita, Noriyuki Kijima, Yoshihiro Oka, Soyoko Morimoto, Hiroko Nakajima, Satoshi Morita, Junichi Sakamoto, Sumiyuki Nishida, Naoki Hosen, Yusuke Oji, Norio Arita, Toshiki Yoshimine, Haruo Sugiyama
  • Journal Title: Cancer Immunology Immunotherapy Volume: - Issue: 6 Pages: 707-16
  • DOI: 10.1007/s00262-015-1674-8
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Wilms tumor gene (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer. (2014)
  • Author(s): Nishida S, Koido S et al
  • Journal Title: J Immunother Volume: 37 Issue: 2 Pages: 105-114
  • DOI: 10.1097/cji.0000000000000020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Maintenance of complete remission after allogeneic stem cell transplantation in leukemia patients treated with Wilms tumor 1 peptide vaccine (2013)
  • Author(s): Maeda T, Hosen N, Fukushima K, Tsuboi A, Morimoto S, Matsui T, Sata H, Fujita J, Hasegawa K, Nishida S, Nakata J, Nakae Y, Takashima S, Nakajima H, Fujiki F, Tatsumi N, Kondo T, Hino M, Oji Y, Oka Y, Kanakura Y, Kumanogoh A, Sugiyama H
  • Journal Title: Blood Cancer J Volume: 3 Issue: 8 Pages: e130-e130
  • DOI: 10.1038/bcj.2013.29
  • Peer Reviewed
• [Journal Article] Functional human Th17 clones with WT1-specific helper activity. (2013)
  • Author(s): Tachino S, Fujiki F, Oka Y, Tsuboi A, Morimoto S, Lin YH, Tamanaka T, Kondo K, Nakajima H, Nishida S, Hosen N, Oji Y, Kumanogoh A, Sugiyama H.
  • Journal Title: Cancer Immunol Immunother. Volume: 62（4） Issue: 4 Pages: 801-10
  • DOI: 10.1007/s00262-012-1385-3
  • Peer Reviewed
• [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: Barcelona, Spain
  • Year and Date: 2014-04-22 – 2014-04-23
• [Presentation] Gemcitabine plus WT1 peptide-based cancer vaccine versus gemcitabine alone for advanced pancreatic cancer: a randomized phase II clinical study in multi-centre-interim analysis (2014)
  • Author(s): Sumiyuki Nishida, Shinichi Egawa, Satoshi Kokura, Takeshi Ishikawa, Shigeo Koido, Sadamu Homma, Soyoko Morimoto, Satoshi Morita, Yoshihiro Oka, Haruo Sugiyama
  • Organizer: The 7th International Conference on WT1 in human neoplasia
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-04-22 – 2014-04-23
• [Presentation] Response assessments in WT1 peptide vaccination an long term results of combined temozolomide therapy (2014)
  • Author(s): Naoya Hashimoto, Akihiro Tsuboi, Yasuyoshi Chiba, Yoshihiro Oka, Soyoko Morimoto, Hiroko Nakajima, Sumiyuki Nishida, Naoki Hosen, Naoki Kagawa, Yusuke Oji, Toshiki Yoshimine, Haruo Sugiyama
  • Organizer: The 7th International Conference on WT1 in human neoplasia
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-04-22 – 2014-04-23
• [Presentation] Wilms' tumor gene 1 (WT1) peptide-based cancer vaccine combined with gemcitabine for patients with advanced pancreatic cancer (2014)
  • Author(s): Shigeo Koido, Sumiyuki Nishida, Sadamu Homma, Yutaka Takeda, Hideo Komita, Satoshi Morita, Toshinori Ito, Soyoko Morimoto, Yoshihiro Oka, Satoru Yanagisawa, Yoichi Toyama, Masahiro Ikegami, Hiroaki Nagano, Toshifumi Ohkusa, Hisao Tajiri, Haruo Sugiyama
  • Organizer: AACR Annual Meeting
  • Place of Presentation: San Diego, CA
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] HLA class II 拘束性WT1特異的T cell Receptor遺伝子導入によるヘルパー活性とキラー活性を有するCD+4 T細胞の作製 (2013)
  • Author(s): 藤木文博，林ユウ宏，勝原晶子，岡芳弘，坪井昭博，青山奈央，谷井里江，中島博子，森本創世子，保仙直毅，尾路祐介，熊ノ郷淳，杉山治夫
  • Organizer: 第41回 日本臨床免疫学会総会
  • Place of Presentation: 海峡メッセ下関