Development of a novel cellular vaccine of GITRL-Fc expressing tumor cells for treatment of patients with advanced malignancy

2011 Fiscal Year Final Research Report

• Project/Area Number: 21591664
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Mie University
• Principal Investigator: IKEDA Hiroaki 三重大学, 大学院・医学系研究科, 准教授 (40374673)
• Co-Investigator(Kenkyū-buntansha): NISHIKAWA Hiroyoshi 大阪大学, 免疫学フロンティア研究センター, 准教授 (10444431)
• Project Period (FY): 2009 – 2011
• Keywords: GITRL / GITRL-Fc / 抗腫瘍免疫 / T細胞マルチファンクション性 / 制御性T細胞 / T細胞移入療法 / 遺伝子療法 / siT+ AV3CRベクター

Research Abstract

Tumor cell vaccine expressing GITRL-Fc and gene therapy with adenovirus encoding GITRL-Fc were found to be effective in cancer immunotherapy. We started a clinical trial with TCR-gene modified T cells that express MAGE-A4-specific TCR for patients with advanced esophageal cancer. Stimulation through integrin molecules and CD4 T cell-help were found to enhance multifunctionality and survival of tumor specific CD8+ T cells.

Research Products

• [Journal Article] T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/gc_null mice (2012)
  • Author(s): Shirakura Y Mizuno Y, Wang L, Imai N, Amaike C, Sato E, Ito M, Nukaya I, Mineno J, Takesako K, Ikeda H, Shiku H
  • Journal Title: Cancer Sci Volume: 103(1) Pages: 17-25
  • Peer Reviewed
• [Journal Article] Intracellular tumor-associated antigens represent effective targets for passive immunotherapy (2012)
  • Author(s): Noguchi T, Kato T, Wang L, Maeda Y, Ikeda H, Sato E, Knuth A, Gnjatic S, Ritter G, Sakaguchi S, Old LJ, Shiku H, Nishikawa H
  • Journal Title: Cancer Res Volume: 72(7) Pages: 1672-1682
  • Peer Reviewed
• [Journal Article] siRNA-mediated silencing of PD-1 ligands enhances tumor-specific human T cell effector functions (2011)
  • Author(s): Iwamura K, Kato T, Miyahara Y, Naota H, Mineno J, Ikeda H, Shiku H
  • Journal Title: Gene Ther
  • DOI: doi:10.1038/gt.2011.185
  • Peer Reviewed
• [Journal Article] Association of CD8^+ T cell infiltration in esophageal carcinomalesions with HLA class I antigen expression and survival (2011)
  • Author(s): Tsuchikawa, T, Ikeda H, Cho Y, Miyamoto M, Shichinohe, T, Hirano S, Kondo S
  • Journal Title: Clin Exp Immunol Volume: 164(1) Pages: 50-6
  • Peer Reviewed
• [Journal Article] Improved expression and reactivity of transduced tumor-specific TCRs in human lymphocytes by silencing of endogenous TCR (2009)
  • Author(s): Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I
  • Journal Title: Cancer Res Volume: 69(23) Pages: 9003-11
  • Peer Reviewed
• [Journal Article] Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan(CHP)-NY-ESO-1 and CHP-HER2 with OK-432 (2009)
  • Author(s): Aoki M, Ueda S, Nishikawa H, Kitano S, Hirayama M, Ikeda H, Toyoda H, Tanaka K, Kanai M, Takabayashi A, Imai H, Shiraishi T, Sato E, Wada H, Nakayama E, Takei Y, Katayama N, Shiku H, Kageyama S
  • Journal Title: Vaccine Volume: 7(49) Pages: 6854-61
  • Peer Reviewed
• [Journal Article] GITR stimulation enhances multifunctionality of adoptively transferred tumor antigen-specific CD8^+ T cells with tumor regression (2009)
  • Author(s): Imai N, Ikeda H, Tawara I, Wang L, Wang L, Nishikawa H, Kato T, Shiku H
  • Journal Title: Cancer Sci Volume: 100(7) Pages: 1317-1325
  • Peer Reviewed
• [Presentation] ANTIGEN RECEPTOR GENE-MODIFIED LYMPHOCYTES : HARNESSING T CELLS FOR EFFECTIVE CANCER TREATMENT (2011)
  • Author(s): Hiroaki Ikeda, Naoko Imai, Hayato Hosoi, Makiko Yamane, Sachiko Okamoto, Junichi Mineno, Shinichi Kageyama, Kazutoh Takesako, Hiroshi Shiku
  • Organizer: 第17回日本遺伝子治療学会2011年次学術集会招待講演
  • Place of Presentation: 福岡
  • Year and Date: 20110715-17
• [Presentation] 遺伝子改変T細胞輸注療法 (2011)
  • Author(s): 池田裕明、今井奈緒子、細井勇人、山根真妃子、岡本幸子、峰野純一、竹迫一任、影山慎一、珠玖洋
  • Organizer: 第15回日本がん免疫学会総会招待講演
  • Place of Presentation: 大阪
  • Year and Date: 20110630-0701
• [Presentation] Gene-modified T cell therapy : Harnessing lymphocytes for effective cancer treatment (2011)
  • Author(s): Hiroaki Ikeda, Naoko Imai, Hayato Hosoi, Makiko Yamane, Sachiko Okamoto, Junichi Mineno, Kazutoh Takesako, Shinichi Kageyama, Hiroshi Shiku
  • Organizer: 第70回日本癌学会学術総会招待講演
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] がん特異的T細胞輸注療法の新展開 (2010)
  • Author(s): 池田裕明、今井奈緒子、王立楠、細井勇人、岡本幸子、峰野純一、影山慎一、珠玖洋
  • Organizer: 第31回日本臨床薬理学会年会招待講演
  • Place of Presentation: 京都
  • Year and Date: 20101201-03
• [Presentation] Gene-Modified Lymphocytes : Harnessing T Cells for Effective Cancer Treatment. International Society for Cell Therapy (2010)
  • Author(s): Ikeda H, Okamoto S, Mineno J, Imai N, Kageyama S, Ito M, Yasukawa M, Takesako K, Shiku H
  • Organizer: 1^<st> Asia-Pacific Regional Meeting,招待講演
  • Place of Presentation: Miyazaki, Japan
  • Year and Date: 20101017-20
• [Presentation] Interaction with fibronectin fragment(RetroNectin) on TCR stimulation enhances proliferation and survival of human peripheral T cells (2010)
  • Author(s): Hosoi H, Ikeda H, Hyuga C, Orito Y, Nukaya I, Enoki R, Mineno J, Takesako K, Kondo S, Shiku H
  • Organizer: CRI symposium 2010
  • Place of Presentation: NY, USA
  • Year and Date: 20101006-08
• [Presentation] A novel STAT3 inhibitor reverses tumor-associated immunosuppression and enhances the efficacy of adoptive T cell therapy of cancer (2010)
  • Author(s): Ikeda H, Sugiyama D, Muraoka D, Imai N, Harada N, Akiyama Y, Asai A, Shiku H
  • Organizer: International Society of Biological Therapy of Cancer, Annual Meeting 2010
  • Place of Presentation: Washington D. C., USA
  • Year and Date: 20101002-04
• [Presentation] GENE-MODIFIED LYMPHOCYTES : A TRANSLATIONAL BRIDGE TO EFFECTIVE T CELL THERAPY OF CANCER (2010)
  • Author(s): Ikeda H, Okamoto S, Mineno J, Imai N, Kageyama S, Ito M, Yasukawa M, Takesako K, Shiku H
  • Organizer: 第16回日本遺伝子治療学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 20100701-03
• [Presentation] CD8^+細胞傷害性T細胞の制御によるがん免疫療法 (2010)
  • Author(s): 池田裕明、今井奈緒子、岡本幸子、峰野純一、影山慎一、珠玖洋
  • Organizer: 第20回日本サイトメトリー学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 20100626-27
• [Presentation] Shiku H CD4^+ T cell help on the induction of functional tumor-specific CD8^+ T cells with survival marker (2010)
  • Author(s): Imai N, Ikeda H, Tawara I, Mori K, Yamane M, Wang L
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-23
• [Presentation] Improved expression and anti-tumor reactivity of transduced tumor-specific TCRs in human lymphocytes by specific silencing of endogenous TCR (2009)
  • Author(s): Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I
  • Organizer: CRI symposium 2009
  • Place of Presentation: NY, USA
  • Year and Date: 20091030-1002
• [Presentation] Specific silencing of endogenous TCR with siRNAs in human lymphocytes improved expression and anti-tumor reactivity of transduced tumor-specific TCRs (2009)
  • Author(s): Okamoto S, Mineno J, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I
  • Organizer: 24^<th> Annual Meeting of iSBTc
  • Place of Presentation: Washington, D. C., USA
  • Year and Date: 20091029-31
• [Presentation] Adoptive immunotherapy for cancer with genetically engineered T cells「遺伝子改変T細胞移入療法」 (2009)
  • Author(s): Ikeda H, Okamoto S, Mineno J, Imai N, Ito M, Yasukawa M, Takesako K, Shiku H
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20091023-25
• [Presentation] Multistage activation of tumor-specific CD8^+ T cells by intratumor secretion of GITRL-Fc「GITRL-Fc分泌型融合蛋白の腫瘍内発現による腫瘍特異的T細胞の多層的活性化機構」 (2009)
  • Author(s): Mitsui J, Ikeda H, Hosoi H, Mineno J, KatoI, Kondo S, Shiku H
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 20091001-03
• [Presentation] CD^<4+> T cells play a critical role in the induction of multifunctionality of tumor-specific CD8^+ T cells resulting in effective tumor eradication (2009)
  • Author(s): Imai N, Ikeda H, Tawara I, Mori K, Yamane M, Wang L, Shiku H
  • Organizer: CRI symposium 2009
  • Place of Presentation: NY, USA
  • Year and Date: 20090930-1002
• [Presentation] A critical role for the multifunctionality of anti-tumor human T cells in TCR gene therapy evaluated in an in vivo model utilizing NOG mice (2009)
  • Author(s): Mizuno Y, Ikeda H, Shirakura Y, Hiasa A, Hyuga C, Wang L, Imai N, Sato E, Ito M, Yu S, Mineno J, Kato I, Shiku H
  • Organizer: CRI symposium 2009
  • Place of Presentation: NY, USA
  • Year and Date: 20090930-1002
• [Presentation] GITRL-Fc分泌型融合蛋白の腫瘍内発現による腫瘍抗原特異的T細胞の活性化機構 (2009)
  • Author(s): 池田裕明、三井潤、峰野純一、加藤郁之進、珠玖洋
  • Organizer: 第13回日本がん免疫学会総会
  • Place of Presentation: 小倉
  • Year and Date: 20090624-25
• [Book] Immunotherapy (2012)
  • Author(s): Ikeda H
  • Total Pages: 241-4
• [Book] ドラッグデリバリーシステムの新展開II (2012)
  • Author(s): 珠玖洋、原田直純、池田裕明
  • Total Pages: 128-135
  • Publisher: シーエムシー出版
• [Book] Immunotherapeutic approaches (2011)
  • Author(s): Ikeda H, Shiku H
  • Total Pages: 1-14
  • URL: http://www.landesbioscience.com/curie/
• [Book] がん生物学イラストレイテッド (2011)
  • Author(s): 今井奈緒子、池田裕明、珠玖洋
  • Total Pages: 260-269
  • Publisher: 羊土社
• [Book] 日本臨床 (2011)
  • Author(s): 池田裕明、珠玖洋
  • Total Pages: 1530-1533
• [Book] 臨床薬理 (2011)
  • Author(s): 池田裕明
  • Total Pages: 135-136
• [Book] CTL-がん免疫療法-実用化へのチャレンジ (2010)
  • Author(s): 池田裕明
  • Total Pages: 104-114
  • Publisher: シーエムシー出版
• [Book] 遺伝子診断学 (2010)
  • Author(s): 池田裕明、今井奈緒子、珠玖洋
  • Total Pages: 634-640
• [Book] SURGERY FRONTIER (2010)
  • Author(s): 今井奈緒子、池田裕明、岡本幸子、峰野純一、珠玖洋
  • Total Pages: 65-70
• [Book] 免疫異常 (2009)
  • Author(s): 池田裕明、珠玖洋
  • Publisher: 中山書店
• [Book] 最新医学 (2009)
  • Author(s): 池田裕明
  • Total Pages: 2420-2427
• [Book] 実験医学 (2009)
  • Author(s): 池田裕明、珠玖洋
  • Total Pages: 2176-2184
• [Remarks]
  • URL: http://www.shikuken.jp/
• [Patent(Industrial Property Rights)] T細胞の機能増強方法 (2010)
  • Inventor(s): 珠玖洋、池田裕明、岩村康一、峰野純一、加藤郁之進
  • Industrial Property Rights Holder: 国立大学法人三重大学、タカラバイオ株式会社
  • Industrial Property Number: PTC特許
  • Filing Date: 2010-03-06
  • Overseas