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Development of the vaccinotherapy with HDAC inhibitor regulating immunoescape

Research Project

Project/Area Number 22659235
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionSapporo Medical University

Principal Investigator

HIRATA Kouichi  札幌医科大学, 医学部, 教授 (50136959)

Co-Investigator(Kenkyū-buntansha) SATO Noriyuki  札幌医科大学, 医学部, 教授 (50158937)
TORIGOE Toshihiko  札幌医科大学, 医学部, 准教授 (20301400)
FURUHATA Tomohisa  札幌医科大学, 医学部, 准教授 (80359992)
OHMURA Tosei  札幌医科大学, 医学部, 特任准教授 (30295349)
KAMESHIMA Hidekazu  札幌医科大学, 医学部, 助教 (80517912)
KIMURA Yasutoshi  札幌医科大学, 医学部, 講師 (80311893)
KUTOMI Goro  札幌医科大学, 医学部, 助教 (10404625)
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywords癌ワクチン / 腫瘍免疫 / ペプチド / HDAC / 癌治療
Research Abstract

Cancer vaccine therapy utilizing surviving 2B peptide had been indicated for the patients with unresectable advanced or recurrent cancers during recent two years between 2010 April and 2012 March. Totally, eight patients with gastrointestinal or mammary cancers had been registered and treated under the strict maintenance by the clinical research protocol. No revere adverse effect had been experienced, but slight fever(grade II) was observed in two patients and typical skin reactions just on/in the dermal injection sites of peptide was mostly yielded but no severe allergic reaction and no ulcer formation was noted. Therefore, clinical trials by the protocol had been established. Immunological response was clearly admitted in most of patients. Clinical effect was SD in six patients and PD in two patients.
The low or negative expression of MHC class I in cancer cell wall indicated no immunological effect for those cells, as one of escape mechanisms. The HDAC inhibitors have the promotion effect on the expression of MHC class I, then HDAC inhibitor pretreatment before vaccine administration was tried. The patients with the indications were registered at the end of this protocol schedule, then now is ongoing as the phase I and II. Grade I adverse effects(nausea and elevation of hepatic transaminase) were noticed but it was possible to continue under this protocol.
Further investigation would be established within one year.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (44 results)

All 2012 2011 2010

All Journal Article (30 results) (of which Peer Reviewed: 29 results) Presentation (13 results) Book (1 results)

  • [Journal Article] ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells2012

    • Author(s)
      Matsuzaki J, Torigoe T, Hirohashi Y, Kamiguchi K, Tamura Y, Tsukahara T, Kubo T, Takahashi A, Nakazawa E, Saka E, Takahashi S, Sato N
    • Journal Title

      Carcinogenesis

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses2012

    • Author(s)
      Mizuuchi M, Hirohashi Y, Torigoe T, Kuroda T, Yasuda K, Shimizu Y, Saito T, Sato N
    • Journal Title

      Exp Mol Pathol

      Volume: 92(1) Pages: 185-90

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population2012

    • Author(s)
      Mori T, Nishizawa S, Hirohashi Y, Torigoe T, Tamura Y, Takahashi A, Kochin V, Fujii R, Kondo T, Greene MI, Hara I, Sato N
    • Journal Title

      Exp Mol Pathol

      Volume: 92(1) Pages: 27-32

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] SOX2 is expressed in stem-like cells of human lung adenocarcinoma and augments the tumor-initiating potential2011

    • Author(s)
      Nakatsugawa, M., Takahashi, A., Hirohashi, Y., Torigoe, T., Inoda, S., Asanuma, H., Tamura, Y., Hasegawa, T., Takahashi, H., and Sato, N.
    • Journal Title

      Lab Invest.

      Volume: 91 Issue: 12 Pages: 1796-1804

    • DOI

      10.1038/labinvest.2011.140

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-associated dendritic cells : molecular mechanisms to suppress antitumor immunity2011

    • Author(s)
      Hirohashi Y, Sato N
    • Journal Title

      Immunotherapy

      Volume: 3(8) Pages: 945-7

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma2011

    • Author(s)
      Kano, M., Tsukahara, T., Emori, M., Murase, M., Torigoe, T., Kawaguchi, S., Wada, T., Yamashita, T., Sato, N.
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 8 Pages: 1443-1137

    • DOI

      10.1111/j.1349-7006.2011.01962.x

    • NAID

      10030241866

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma2011

    • Author(s)
      Tanaka, T., Kitamura, H., Torigoe, T., Hirohashi, Y., Masumori, N., Sato, N. and Tsukamoto, T.
    • Journal Title

      J. Cancer Res. Clin. Oncol.

      Volume: 137(5) Pages: 789-94

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells2011

    • Author(s)
      Inoda S, Hirohashi Y, Torigoe T, Morita R, Takahashi A, Asanuma H, Nakatsugawa M, Nishizawa S, Tamura Y, Tsuruma T, Terui T, Kondo T, Ishitani K, Hasegawa T, Hirata K, Sato N
    • Journal Title

      Am J Pathol

      Volume: 178(4) Pages: 1805-13

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells2011

    • Author(s)
      Oura J, Tamura Y, Kamiguchi K, Kutomi G, Sahara H, Torigoe T, Himi T, Sato N
    • Journal Title

      Int Immunol

      Volume: 23(4) Pages: 223-37

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of speedy PCR-ssp method and serological typing of HLA-A24 for Japanese cancer patients2011

    • Author(s)
      Nakatsugawa M, Hirohashi Y, Torigoe T, Inoda S, Kiriyama K, Tamura Y, Sato E, Takahashi H, Sato N
    • Journal Title

      J Immunoassay Immunochem

      Volume: 32(2) Pages: 93-102

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients2011

    • Author(s)
      Kameshima H, Tsuruma T, Torigoe T, Takahashi A, Hirohashi Y, Tamura Y, Tsukahara T, Ichimiya S, Kanaseki T, Iwayama Y, Sato N, Hirata K
    • Journal Title

      Cancer Sci

      Volume: 102(6) Pages: 1181-7

    • NAID

      10029294487

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-produced secreted form of binding of immunoglobulin protein elicits antigen-specific tumor immunity2011

    • Author(s)
      Tamura Y, Hirohashi Y, Kutomi G, Nakanishi K, Kamiguchi K, Torigoe T, Sato N
    • Journal Title

      J Immunol

      Volume: 186(7) Pages: 4325-30

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-Produced Secreted Form of Binding of Immunoglobulin Protein Elicits Antigen-Specific Tumor Immunity.2011

    • Author(s)
      Tamura Y, Hirohashi Y, Kutomi G, Nakanishi K, Kamiguchi K, Torigoe T, Sato N.
    • Journal Title

      J. Immunol

      Volume: 186 Issue: 7 Pages: 4325-4330

    • DOI

      10.4049/jimmunol.1004048

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular heat shock protein 90 plays a role in translocating chaper oned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells2011

    • Author(s)
      Oura J, et al
    • Journal Title

      Int.Immunol

      Volume: 23 Issue: 4 Pages: 223-237

    • DOI

      10.1093/intimm/dxr013

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma2011

    • Author(s)
      Inoda S, Morita R, Hirohashi Y, Torigoe T, Asanuma H, Nakazawa E, Nakatsugawa M, Tamura Y, Kamiguchi K, Tsuruma T, Terui T, Ishitani K, Hashino S, Wang Q, Greene MI, Hasegawa T, Hirata K, Asaka M, Sato N.
    • Journal Title

      Exp. Mol. Pathol.

      Volume: 90 Issue: 1 Pages: 55-60

    • DOI

      10.1016/j.yexmp.2010.10.001

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells2011

    • Author(s)
      Inoda S, et al
    • Journal Title

      Am.J.Pathol.

      Volume: 178 Pages: 1805-1813

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients2011

    • Author(s)
      Kameshima, H., Tsuruma, T., Torigoe, T., Takahashi, A., Hirohashi, Y., Tamura, Y., Tsukahara, T., Ichimiya, S., Kanaseki, T., Iwayama, Y., Sato, N., Hirata, K.
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 6 Pages: 1181-1187

    • DOI

      10.1111/j.1349-7006.2011.01918.x

    • NAID

      10029294487

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor associated dendritic cells : molecular mechanisms to suppress anti-tumor immunity2011

    • Author(s)
      Hirohashi, Y. and Sato, N.
    • Journal Title

      Immunotherapy

      Volume: 3 Issue: 8 Pages: 945-947

    • DOI

      10.2217/imt.11.94

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer2011

    • Author(s)
      Miyazaki A, Kobayashi J, Torigoe T, Hirohashi Y, Yamamoto T, Yamaguchi A, Asanuma H, Takahashi A, Michifuri Y, Nakamori K, Nagai I, Sato N, Hiratsuka H.
    • Journal Title

      Cancer Sci

      Volume: 102 Issue: 2 Pages: 324-329

    • DOI

      10.1111/j.1349-7006.2010.01789.x

    • NAID

      10029289826

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of speedy PCR-ssp method and serological typing of hla-a24 for Japanese cancer patients.2011

    • Author(s)
      Nakatsugawa M, Hirohashi Y, Torigoe T, Inoda S, Kiriyama K, Tamura Y, Sato E, Takahashi H, Sato N.
    • Journal Title

      J Immunoassay Immunochem

      Volume: 32 Issue: 2 Pages: 93-102

    • DOI

      10.1080/15321819.2010.543219

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma2011

    • Author(s)
      Tanaka, T., Kitamura, H., Torigoe, T., Hirohashi, Y., Masumori, N., Sato, N. and Tsukamoto, T.
    • Journal Title

      J. Cancer Res. Clin. Oncol

      Volume: 137 Issue: 5 Pages: 789-794

    • DOI

      10.1007/s00432-010-0940-6

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tumor-Produced Secreted Form of Binding of Immunoglobul in Protein Elicits Antigen-Specific Tumor Immunity.2011

    • Author(s)
      Tamura Y, et al.
    • Journal Title

      J.Immunol

      Volume: 186 Pages: 4325-4330

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular heat shock protein 90 plays a role in translocating chaperoned antigen from endosome to proteasome for generating antigenic peptide to be cross-presented by dendritic cells.2011

    • Author(s)
      Oura. J, et al.
    • Journal Title

      Int.Immunol

      Volume: 23 Pages: 223-237

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogenic enhancement and clinical effect by type-I interferon of anti-apoptotic protein, survivin-derived peptide vaccine, in advanced colorectal cancer patients.2011

    • Author(s)
      Kameshima. H, et al.
    • Journal Title

      Cancer Sci

      Volume: March Issue(in press)

    • NAID

      10029294487

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytotixic T lymphocytes efficiently recognize human colon cancer stem-like cells.2011

    • Author(s)
      Inoda. S, et al.
    • Journal Title

      Am.J.Pathol.

      Volume: 178 Pages: 1805-1813

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma.2011

    • Author(s)
      Inoda. S, et al.
    • Journal Title

      Experimental and molecular pathology

      Volume: 90 Pages: 55-60

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells.2011

    • Author(s)
      Inoda. S, et al.
    • Journal Title

      Am J Pathol

      Volume: 178 Pages: 1805-1813

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma.2011

    • Author(s)
      Inoda. S, et al.
    • Journal Title

      Exp Mol Pathol

      Volume: 90 Pages: 55-60

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spatiotemporal regulation of heat shock protein 90-chaperoned self-DNA and CpG-oligodeoxynucleotide for type I IFN induction via targeting to static early endosome.2010

    • Author(s)
      Okuya. K, et al.
    • Journal Title

      J.Immunol

      Volume: 184 Pages: 7092-7099

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] がん治療の新たな展開 4.癌ワクチン・免疫療法2010

    • Author(s)
      平田公一, 他
    • Journal Title

      北海道医報

      Volume: 1102 Pages: 12-17

    • Related Report
      2010 Annual Research Report
  • [Presentation] HSP-癌ペプチド複合体ワクチンの高CTL誘導性機構の解析と治療への応用2011

    • Author(s)
      九冨五郎
    • Organizer
      第24回日本バイオセラピイ学会
    • Place of Presentation
      和歌山
    • Year and Date
      2011-12-01
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 進行・再発膵癌に対するサバイビン2Bペプチドによるワクチン療法2011

    • Author(s)
      九冨五郎
    • Organizer
      第49回日本癌治療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-29
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] がん幹細胞の免疫学的特性とワクチンの開発2011

    • Author(s)
      鳥越俊彦
    • Organizer
      がん免疫学会シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2011-06-30
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 難治がんに対するペプチドワクチン療法:現状と課題2011

    • Author(s)
      鳥越俊彦
    • Organizer
      北海道癌談話会シンポジウム
    • Place of Presentation
      札幌
    • Year and Date
      2011-06-25
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] がん組織の微小環境と免疫2011

    • Author(s)
      鳥越俊彦
    • Organizer
      第100回日本病理学会学術集会シンポジウム
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-28
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] がん幹細胞の免疫学的特性とワクチンの開発2011

    • Author(s)
      鳥越俊彦
    • Organizer
      第13回癌治療増感研究シンポジウム
    • Place of Presentation
      奈良
    • Year and Date
      2011-02-11
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] 大腸癌原発巣におけるHLAクラスI発現は予後規定因子となりうるか2010

    • Author(s)
      鶴間哲弘, 他
    • Organizer
      第73回大腸癌研究会
    • Place of Presentation
      鹿児島県奄美市
    • Year and Date
      2010-07-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] サバイビン 2Bペプチドワクチン療法:より効果的な免疫反応と治療効果をめざして2010

    • Author(s)
      亀嶋秀和, 他
    • Organizer
      第48回日本癌治療学会学術集会パネルディスカッション4
    • Place of Presentation
      京都府
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hypoxia-inducible human endoplasmic reticulum oxidoreduction 1-La (hEro1-La) regulates the expression of MHC class I and II molecules.2010

    • Author(s)
      K.Saito, et al.
    • Organizer
      14^<th> International Congress on Immunology, Kobe
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2010 Annual Research Report
  • [Presentation] MHC class I expression is down-regulated through epithelial-mesenchymal transition of breast cancer.2010

    • Author(s)
      T.Torigoe, et al.
    • Organizer
      14^<th> International Congress on Immunology
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2010 Annual Research Report
  • [Presentation] サバイビン2Bペプチドワクチン療法:より効果的な免疫反応と臨床効果をめざして2010

    • Author(s)
      亀嶋秀和, 他
    • Organizer
      第48回日本癌治療学会学術集会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2010 Annual Research Report
  • [Presentation] 乳がんに対する免疫療法最前線:がん幹細胞抗原と免疫逃避の制御2010

    • Author(s)
      鳥越俊彦, 他
    • Organizer
      第18回日本乳癌学会学術総会
    • Place of Presentation
      北海道札幌市
    • Related Report
      2010 Annual Research Report
  • [Presentation] サバイビン2Bペプチドによるワクチン療法:最適なアジュバントにより効果的な免疫反応と臨床効果をめざして2010

    • Author(s)
      亀嶋秀和, 他
    • Organizer
      第14回日本がん免疫学会総会
    • Place of Presentation
      熊本県熊本市
    • Related Report
      2010 Annual Research Report
  • [Book] Targeting survivin in cancer therapy : Clinical considerations. Apoptosome An up-and-coming_therapeutical tool.2010

    • Author(s)
      Tsuruma. T, et al.
    • Total Pages
      322
    • Publisher
      Springer. Francesco Cecconi Marcello D'Amelio Editors
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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