Development of a novel cancer immunotherapy based on efficient induction of memory T cells.

• Project/Area Number: 24700991
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor immunology
• Research Institution: Osaka University
• Principal Investigator: FUJIKI Fumihiro 大阪大学, 医学(系)研究科(研究院), 特任助教 (40456926)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: メモリーT細胞 / 癌免疫療法 / WT1 / CTL / ヘルパーT細胞 / ヘルパーＴ細胞 / メモリーＴ細胞 / エフェクターーＴ細胞 / マスター遺伝子

Research Abstract

The induction of tumor-associated antigens (TAAs)-specific memory T cell and its maintenance are essential for ideal cancer immunotherapy. However, mechanism of memory T cell development remains unclear. In this study, we investigated the role of gene A in a murine Listeria monocytogenes infection model. As expected, gene A-deficient T cells exhibited high level of CD127 and CD62L expression after infection, leading to enhanced memory T cell formation. In addition, gene A-deficient memory T cells showed enhanced proliferative response after secondary infection.

Research Products

• [Journal Article] The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers. (2014)
  • Author(s): Oji Y, Tatsumni N, Izumoto S (34 名省略）
  • Journal Title: Int J Oncol Volume: 44 Issue: 5 Pages: 1461-1469
  • DOI: 10.3892/ijo.2014.2318
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens. (2013)
  • Author(s): Yatsuda J, Irie A, Harada K, Michibata Y, Tsukamoto H, Senju S, Tomita Y, Yuno A, Hirayama M, Abu Sayem M, Takeda N, Shibuya I, Sogo S, Fujiki F, Sugiyama H, Eto M, Nishimura Y.
  • Journal Title: PLoS One Volume: 8 Issue: 12 Pages: e84908-e84908
  • DOI: 10.1371/journal.pone.0084908
  • Peer Reviewed
• [Journal Article] HLA-DPB1*05: 01-restricted WT1332-specific TCR-transduced CD4+ T lymphocytes display a helper activity for WT1-specific CTL induction and a cytotoxicity against leukemia cells. (2013)
  • Author(s): Lin Y, Fujiki F, Katsuhara A, Oka Y, Tsuboi A, Aoyama N, Tanii S, Nakajima H, Tatsumi N, Morimoto S, Tamanaka T, Tachino S, Hosen N, Nishida S, Oji Y, Kumanogoh A, Sugiyama H.
  • Journal Title: J Immunother. Volume: 36（3） Issue: 3 Pages: 159-70
  • DOI: 10.1097/cji.0b013e3182873581
  • 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
• [Journal Article] Identification of a Wilms' tumor1-derived immunogenic CD4(+) T-cell epitope that is recognized in the context of common Caucasian HLA-DR haplotypes (2013)
  • Author(s): Anguille S, Fujiki F, et al
  • Journal Title: Leukemia Volume: 27 Issue: 3 Pages: 748-50
  • DOI: 10.1038/leu.2012.248
  • Peer Reviewed
• [Journal Article] In vivo eradication of MLL/ENL leukemia cells by NK cells in the absence of adaptive immunity. (2013)
  • Author(s): Nakata J, Nakano K, Okumura A, Mizutani Y, Kinoshita H, Iwai M, Hasegawa K, Morimoto S, Fujiki F, Tatsumi N, Nakajima H, Nakae Y, Nishida S, Tsuboi A, Oji Y, Oka Y, Sugiyama H, Kumanogoh A, Hosen N.
  • Journal Title: Leukemia. Volume: - Issue: 6 Pages: 1316-1325
  • DOI: 10.1038/leu.2013.374
  • Peer Reviewed
• [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] Recognition of a natural WT1 epitope by a modified WT1 peptide-specific T-cell receptor (2012)
  • Author(s): Tamanaka T, Oka Y, Fujiki F, et al
  • Journal Title: Anticancer Res Volume: 32 Pages: 5201-9
  • URL: http://ar.iiarjournals.org/content/32/12/5201
  • Peer Reviewed
• [Journal Article] Recognition of a natural WT1 epitope by a modified WT1 peptide-specific T-cell receptor (2012)
  • Author(s): Tamanaka T, Oka Y, Fujiki F, Tsuboi A, Katsuhara A, Nakajima H, Hosen N, Nishida S, Lin YH, Tachino S, Akatsuka Y, Kuzushima K, Oji Y, Kumanogoh A, Sugiyama H
  • Journal Title: Anticancer Research Volume: 32 Pages: 5201-5209
  • Peer Reviewed
• [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CD4+T 細胞の作製 (2013)
  • Author(s): 藤木文博, 等
  • Organizer: 第41回日本臨床免疫学会総会
  • Place of Presentation: 海峡メッセ下関
  • Year and Date: 2013-11-28
  • Invited
• [Presentation] HLA-DPB1*05 : 01 拘束性WT1 特異的TCR を導入されたCD4+T細胞はヘルパー活性と細胞傷害活性を有する (2013)
  • Author(s): 藤木文博, 等
  • Organizer: 第17回日本がん免疫学会総会
  • Place of Presentation: ANA クラウンプラザホテル宇部
  • Year and Date: 2013-07-04
• [Presentation] HLA class II-restricted WT1-specific TCR-transduced CD4+ T cells display a helper activity for WT1-specific CTL induction and acytotoxicity against leukemia cells (2013)
  • Author(s): Fujiki F, et al
  • Organizer: The 4th JSH International Symposium 2013
  • Place of Presentation: YAMATOTA-HONTEN, Ehime
  • Year and Date: 2013-05-24
• [Presentation] HLA class II-restricted WT1-specific TCR-transduced CD4+ T cells display a helper activity for WT1-specific CTL induction and a cytotoxicity against leukemia cells. (2013)
  • Author(s): Fumihiro Fujiki, Yuhung Lin, Akiko Katsuhara, Yoshihiro Oka, Akihiro Tsuboi, Nao Aoyama, Satoe Tanii, Hiroko Nakajima, Naoya Tatsumi, Soyoko Morimoto, Naoki Hosen, Sumiyuki Nishida, Yusuke Oji, Atsushi Kumanogoh and Haruo Sugiyama
  • Organizer: The 4th JSH International symposium 2013
  • Place of Presentation: YAMATOYA-HONTEN, Ehime
• [Presentation] HLA-DPB1*05:01拘束性WT1特異的TCRを導入されたCD4+T細胞はヘルパー活性と細胞傷害活性を有する (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、西田純幸、尾路祐介、熊ノ郷淳、杉山治夫
  • Organizer: 第17回日本がん免疫学会総会
  • Place of Presentation: ANAクラウンプラザホテル宇部
• [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CD4+ 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
  • Invited
• [Presentation] Cancer antigen WT1-specific helper and suppressive Th17 derived from a single precursor cell (2012)
  • Author(s): Tachino Sho, Oka Yoshihiro, Fumihiro Fujiki, Tsuboi Akihiro, Tamanaka Taichi, Kondo Kenta, Hosen Naoki, Oji Yusuke, Kumanogoh Atsushi, Sugiyama Haruo
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Biased usage of T cell receptor beta-chain variable region genes of cancer antigen WT1-specific CTLs in patients with solid tumors and healthy donors (2012)
  • Author(s): Morimoto Soyoko, Oka Yoshihiro, Tsuboi Akihiro, Fujiki Fumihiro, Nakajima Hiroko, Hosen Naoki, Oji Yusuke, Kumanogoh Atsushi, Sugiyama Haruo
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Development of HLA-DR4 transgenic mice useful for identification of CD4+ T cell epitope of tumor-associated antigens (2012)
  • Author(s): Yatsuda Junji, Irie Atsushi, Michibata Yayoi, Harada Kumiko, Tomita Yusuke, Yuno Akira, Takeda Naoki, Shibuya Isao, Sogo Shinji, Fujiki Fumihiro, et al
  • Organizer: 日本免疫学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] CD4＋T細胞が認識するがん抗原ペプチドを迅速に同定できるHLA-DR4トランスジェニックマウスの樹立 (2012)
  • Author(s): Yatsuda Junji, Irie Atsushi, Michibata Yayoi, Harada Kumiko, Tomita Yusuke, Yuno Akira, Takeda Naoki, Shibuya Isao, Sogo Shinji, Fujiki Fumihiro, et al
  • Organizer: 日本癌学会
  • Place of Presentation: Royton Sapporo
• [Presentation] Establishment of HLA-DR4 transgenic mice useful for rapid screening of HLA-DR4-restricted CD4+ T cell epitope peptides (2012)
  • Author(s): Irie Atsushi, Yatsuda Junji, Michibata Yayoi, Harada Kumiko, Takeda Naoki, Shibuya Isao, Sogo Shinji, Fujiki Fumihiro, Sugiyama Haruo, Nishimura Yasuharu
  • Organizer: 日本がん免疫学会
  • Place of Presentation: 北海道大学学術交流会館
• [Presentation] HLA-DR4拘束性CD4+Th細胞に抗原提示機能を有するHLA-DR4トランスジェニックマウスの樹立 (2012)
  • Author(s): 入江厚、矢津田旬二、道端弥生、原田久美子、竹田直樹、澁谷功、十河真司、藤木文博、杉山治夫、西村泰治
  • Organizer: 日本組織適合性学会
  • Place of Presentation: 明治大学駿河台キャンパス アカデミーコモン・リバティタワー
• [Presentation] HLA class II拘束性WT1由来ヘルパーペプチド特異的TCRを導入されたCD4+T細胞はヘルパー活性と細胞傷害活性を有する
  • 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、西田純幸、尾路祐介、熊ノ郷淳、杉山治夫
  • Organizer: 第５回造血器腫瘍免疫療法研究会
  • Place of Presentation: ウインク愛知
• [Patent(Industrial Property Rights)] 抗原特異的ヘルパーT 細胞レセプター遺伝子 (2013)
  • Inventor(s): 杉山治夫、藤木文博
  • Industrial Property Rights Holder: 杉山治夫、藤木文博
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-12
  • Overseas
• [Patent(Industrial Property Rights)] 抗原特異的ヘルパーT細胞レセプター遺伝子 (2013)
  • Inventor(s): 杉山治夫、藤木文博
  • Industrial Property Rights Holder: 杉山治夫、藤木文博
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-12
  • Overseas