Polyvalent cancer vaccine

2009 Fiscal Year Final Research Report

• Project/Area Number: 17016031
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Mie University
• Principal Investigator: SHIKU Hiroshi Mie University, 大学院・医学系研究科, 寄付講座教員・産学官連携講座教員 (80154194)
• Co-Investigator(Kenkyū-buntansha): KAGEYAMA Shinichi 三重大学, 大学院・医学系研究科, 准教授 (80194695)
• Project Period (FY): 2005 – 2009
• Keywords: 癌・精巣抗原 / キラーT細胞 / ヘルパーT細胞 / マルチファンクション性T細胞 / ペプチド抗原 / GITR / TCR遺伝子改変T細胞

Research Abstract

1) Analyses on in vivo kinetics and functions of tumor specific T cells : We found the mechanism of antitumor effect of GITR stimulation and the importance of T cell multifunctionality in antitumor immune response. 2) The verification of polyvalent cancer vaccine in animal models : We verified the enhanced antitumor effect of cancer vaccine by GITR stimulation. We developed TCR gene-modified T cells and verified the effectiveness of adoptive T cell therapy using TCR gene-modified T cells. 3) Identification of antigen peptides for clinical use: We identified the MAGE-A4-, NY-ESO-1-, and SAGE-derived antigen peptides recognized by CD8^+ and CD4^+ T cells.

Research Products

• [Journal Article] Tumor progression inhibits the induction of multifunctionality in adoptively transferred tumor-specific CD8+ T cells (2009)
  • Author(s): Imai N., Ikeda H., Tawara I., Shiku H
  • Journal Title: Eur. J. Immunol 39 Pages: 241-53
  • Peer Reviewed
• [Journal Article] Rapid alphabeta TCR-mediated responses in gammadelta T cells transduced with cancer-specific TCR genes (2009)
  • Author(s): Hiasa A., Nishikawa H., Hirayama M., Kitano S., Okamoto S., Chono H., Yu SS., Mineno J., Tanaka Y., Minato N., Kato I., Shiku H
  • Journal Title: Gene Ther 16 Pages: 620-8
  • Peer Reviewed
• [Journal Article] Glucocorticoid-induced tumor necrosis factor receptor stimulation enhances the 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 100 Pages: 1317-25
  • 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 27 Pages: 6854-61
  • Peer Reviewed
• [Journal Article] Improved Expression and 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
  • Journal Title: Cancer Res 69 Pages: 9003-11
  • Peer Reviewed
• [Journal Article] Differential Regulatory function of resting and preactivated allergen-specific CD4+CD25+ regulatory T cells in Th2-type airway inflammation (2008)
  • Author(s): Saito K., Torii M., Ma N., Tsuchiya T., Wang L., Hori T., Nagakubo D., Nitta N., Kanegasaki S., Hieshima K., Yoshie O., Gabazza EC., Katayama N., Shiku H., Kuribayashi K., Kato T
  • Journal Title: J. Immunol. 181 Pages: 6889-97
  • Peer Reviewed
• [Journal Article] Regulatory T cell-resistant CD8+ T cells induced by glucocorticoid-induced tumor necrosis factor receptor signaling (2008)
  • Author(s): Nishiakwa H., Kato T., Hirayama M., Orito Y., Sato E., Harada N., Gnjastic S., Old LJ., Shiku H
  • Journal Title: Cancer Res 68 Pages: 5948-54
  • Peer Reviewed
• [Journal Article] Induction of immune response against NY-ESO-1 by CHP-NY-ESO-1 vaccination and immune regulation in a melanoma patient (2008)
  • Author(s): Tsuji K., Hamada T., Uenaka A., Wada H., Sato E., Isobe M., Asagoe K., Yamasaki O., Shiku H., Ritter G., Murphy R., Hoffman EW., Old LJ., Nakayama E., Iwatsuki K
  • Journal Title: Cancer Immunol. Immunother 57 Pages: 1429-37
  • Peer Reviewed
• [Journal Article] Humoral immune responses in patients vaccinated with 1-146 HER2 Protein complexed with cholesteryl pullulan nanogel(CHP-HER2) (2008)
  • Author(s): Kageyama S., Kitano S., Hirayama M., Nagata Y., Imai H., Shiraishi T., Akiyoshi K., Scott A., Murphy R., Hoffman E., Old L., Katayama N., Shiku H
  • Journal Title: Cancer Science 99 Pages: 601-7
  • Peer Reviewed
• [Journal Article] Long-term phenotypic, functional and genetic stability of cancer-specific T cell receptor(TCR)αβgenes transduced to CD8^+T cells. (2008)
  • Author(s): Hiasa A., Hirayama M., Nishikawa H., Kitano S., Nukaya I., Yu SS., Mineno J., Kato I., Shiku H.
  • Journal Title: Gene Ther 15 Pages: 695-9
  • Peer Reviewed
• [Journal Article] Induction of regulatory T cell-resistant helper CD4^+T cells by bacterial vector. (2008)
  • Author(s): Nishikawa H., Tsuji T., Jager E., Briones G., Ritter G., Old LJ., Galan JE., Shiku H., Gnjatic S
  • Journal Title: Blood 111 Pages: 1404-12
  • Peer Reviewed
• [Journal Article] Post immune UV-irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses (2008)
  • Author(s): Wang L., Toda M., Saito K., Hori T., Horii T., Shiku H., Kuribayashi K., Kato T
  • Journal Title: Int. Immunology 20 Pages: 57-70
  • Peer Reviewed
• [Journal Article] In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines (2006)
  • Author(s): Nishikawa H., Sato E., Briones G., Chen LM., Matsuo M., Nagata Y., Ritter G., Jager E., Nomura H., Kondo S., Tawara I., Kato T., Shiku H., Old LJ., Galan JE., Gnjatic S
  • Journal Title: J. Clin. Invest 116 Pages: 1946-54
  • Peer Reviewed
• [Journal Article] Generation of peptide-specific CD8(+) T cells by phytohemagglutinin-stimulated antigen-mRNA-transduced CD4(+) T cells (2006)
  • Author(s): Naota H., Miyahara Y., Okumura S., Kuzushima K., Akatsuka Y., Hiasa A., Kitano S., Takahashi T., Yuta A., Majima Y., Shiku H
  • Journal Title: J. Immunol. Methods 314 Pages: 54-66
  • Peer Reviewed
• [Journal Article] HER2-specific T-cell immune responses in patients vaccinated with truncated HER2 protein complexed with nanogels of cholesteryl pullulan (2006)
  • Author(s): Kitano S., Kageyama S., Nagata Y., Miyahara Y., Hiasa A., Naota H., Okumura S., Imai H., Shiraishi T., Masuya M., Nishikawa M., Sunamoto J., Akiyoshi K., Kanematsu T., Scott AM., Murphy R., Hoffman EW., Old LJ., Shiku H
  • Journal Title: Clin. Cancer Res 12 Pages: 7397-405
  • Peer Reviewed
• [Journal Article] Interferon-γcontrols the generation/activation of CD4^+ CD25^+ regulatory T cells in anti-tumor immune response (2005)
  • Author(s): Nishikawa H., Kato T., Tawara I., Ikeda H., Kuribayashi K., Allen PM., Schreiber RD., Old LJ., Shiku H
  • Journal Title: J. Immunol 175 Pages: 4433-40
  • Peer Reviewed
• [Journal Article] Determination of Cellularly Processed HLA-A2402-Restricted Novel CTL Epitopes Derived from Two Cancer Germ line genes, MAGE-A4 and SAGE. Clin (2005)
  • Author(s): Miyahara Y., Naota H., Wang L., Hiasa A., Goto M., Watanabe M., Kitano S., Okumura S., Takemitsu T., Yuta A., Majima Y., Lemonnier FA., Boon T., Shiku H
  • Journal Title: Cancer Res 11 Pages: 5581-9
  • Peer Reviewed
• [Journal Article] Accelerated chemically induced tumor development mediated by CD4^+CD25^+ regulatory T cells in wild-type hosts (2005)
  • Author(s): Nishikawa H., Kato T., Tawara I., Takemitsu T., Saito K., Wang L., Ikarashi Y., Wakasugi H., Nakayama T., Taniguchi M., Kuribayashi K., Old LJ., Shiku H
  • Journal Title: Proc. Natl. Acad. Sci. USA 102 Pages: 9253-7
  • Peer Reviewed
• [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, MinenoJ, Ikeda H, Fujiwara H, Yasukawa M, Shiku H, Kato I
  • Organizer: 24th Annual Meeting of International Society for Biological Therapy of Cancer
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20091028-20091101
• [Presentation] Cancer regression in immunodeficient NOG mice by transfer of human T cellstransduced with MAGE-A4-specificαβtype TCR genes (2008)
  • Author(s): Ikeda H, Shirakura Y, Hiasa A, Hirayama M, Nishikawa H, Sato E, Nukaya I, Yu SS, Mineno J, Ito M, Kato I, Shiku H
  • Organizer: 16th Meeting in the Cancer Research Institute International Cancer Immunotherapy Symposium Siries and the 2008 Meeting of the Cancer Vaccine Consortium
  • Place of Presentation: NY, USA
  • Year and Date: 20080915-20080917
• [Presentation] Appearance of multifunctional CD8+ effector T cell in vivo is a critical determinant of successful tumor eradication (2008)
  • Author(s): Imai N, Ikeda H, Tawara S, Mineno J, Kato I, Shiku H
  • Organizer: 16th Meeting in the Cancer Research Institute International Cancer Immunotherapy Symposium Siries and the 2008 Meeting of the Cancer Vaccine Consortium
  • Place of Presentation: NY, USA
  • Year and Date: 20080915-20080917
• [Presentation] Regulatory T cell-resistant CD8+ T cells induced by GITR signaling (2008)
  • Author(s): Nishikawa H, Kato T, Harada N, Gnjatic S, Ritter G, Old LJ, Shiku H
  • Organizer: 16th Meeting in the Cancer Research Institute International Cancer Immunotherapy Symposium Siries and the 2008 Meeting of the Cancer Vaccine Consortium
  • Place of Presentation: NY, USA
  • Year and Date: 20080915-20080917
• [Presentation] Vaccination with CHP-NY-ESO-1 to esophageal cancer patients elicits high-affinity NY-ESO-1-specific CD8+ CTLs recognizing tumor cells (2008)
  • Author(s): Hirayama M, Nishikawa H, Aoki M, Ueda S, Kanai M, Takabayashi A, Sato E, Kageyam S, Shiku H
  • Organizer: 16th Meeting in the Cancer Research Institute International Cancer Immunotherapy Symposium Siries and the 2008 Meeting of the Canser Vaccine Consortium
  • Place of Presentation: NY, USA
  • Year and Date: 20080915-20080917
• [Presentation] Functional analyses of T cells transduced withMAGE-A4-specificαβtype TCR genes (2008)
  • Author(s): Hirayama M, Hiasa A, Nishikawa H, Shirakura Y, Ikeda H, Kitano S, Tajima K, Nukaya I, Yu SS, Mineno J, Ito M, Kato I, Shiku H
  • Organizer: American Association for Cancer Research 99th Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20080412-20080416
• [Presentation] Rapid ab TCR-mediated responses in gd T cells transduced with cancer-specific TCR genes (2008)
  • Author(s): Hiasa A, Nishikawa H, Hirayama M, Kitano S, Okamoto S, Chono H, Yu SS, Mineno J, Tanaka Y, Minato N, Kato I, Shiku H
  • Organizer: American Association for Cancer Research 99th Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20080412-20080416
• [Presentation] Combination cancer vaccine of CHP-NY-ESO-1 and CHP-HER2 with immuno-adjuvant, OK-432, for chemorefractory metastatic or recurrent esophageal cancer patients (2008)
  • Author(s): Ueda S, Aoki M, Nishikawa H, Hirayama M, Kitano S, Hayashi E, Kanai M, Takabayashi A, Shiku H, Kageyama S
  • Organizer: American Association for Cancer Research 99th Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 20080412-20080416
• [Presentation] GITR stimmulation enhances anti-tumor effect of adoptive cell therapy restoring activation of antigen-specific CD8+ T Cells (2007)
  • Author(s): Imai N, Ikeda H, Nishikawa H, Yamashita Y, Tawara I, Kato T, Shiku H
  • Organizer: 15th Cancer Research Institute Annual symposium
  • Place of Presentation: NY, USA
  • Year and Date: 20071004-20071006
• [Presentation] A clinical trial of CHP-HER2 vaccine with adjuvant GM-CSF:A case representing antigen spreading (2007)
  • Author(s): Kitano S, Kageyama S, Nishikawa H, Hirayama M, Hiasa A, Ikeda H, Old LJ, Shiku H
  • Organizer: 15th Cancer Research Institute Annual symposium
  • Place of Presentation: NY, USA
  • Year and Date: 20071004-20071006
• [Presentation] Humoral immune responses in patients vaccinated with HER2 protein complexed with a novel antigen delivery system of cholesteryl pullulan(CHP-HER2) (2006)
  • Author(s): Kitano S, Hirayama M, Kageyama S, Nagata Y, Nishikawa H, Scott AM, Murphy R, Hoffman EW, Old LJ, Shiku H
  • Organizer: 97TH Annual Meeting of American Association for Cancer Reseach
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20060401-20060405
• [Presentation] Ex vivo generation of human peripheral blood monocyte-derived antigen presenting cells (2006)
  • Author(s): Katayama N, Shiku H
  • Organizer: International Symposium on Molecular Cell Biology of Macrophages and Dendritic Cells 2006
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2006-06-10
• [Book] 内科学書内科学総論 (2009)
  • Author(s): 珠玖洋、池田裕明, 他
  • Total Pages: 34-42
  • Publisher: 中山書店
• [Remarks]
  • URL: http://www.shikuken.jp/
• [Patent(Industrial Property Rights)] 特異的遺伝子の発現方法 (2008)
  • Inventor(s): 峰野純一、岡本幸子、住岡理早、北川正成、珠玖洋、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: 特許・WO2008/153029(国際公開番号)
  • Filing Date: 2008-06-10
• [Patent(Industrial Property Rights)] 細胞傷害性Tリンパ球 (2004)
  • Inventor(s): 珠玖洋、日浅厚則、奥村悟司、直田浩明、宮原慶裕
  • 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: 特許・特願2004-290785、特開2006-101735
  • Filing Date: 2004-10-01