Development of the vaccinotherapy with HDAC inhibitor regulating immunoescape

• Project/Area Number: 22659235
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Sapporo 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: ¥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.

Research Products

• [Journal Article] ECRG4 is a negative regulator of caspase-8-mediated apoptosis in human T-leukemia cells (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Novel oligomannose liposome-DNA complex DNA vaccination efficiently evokes anti-HPV E6 and E7 CTL responses (2012)
  • 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
  • Peer Reviewed
• [Journal Article] Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population (2012)
  • 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
  • Peer Reviewed
• [Journal Article] SOX2 is expressed in stem-like cells of human lung adenocarcinoma and augments the tumor-initiating potential (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Tumor-associated dendritic cells : molecular mechanisms to suppress antitumor immunity (2011)
  • Author(s): Hirohashi Y, Sato N
  • Journal Title: Immunotherapy Volume: 3(8) Pages: 945-7
  • Peer Reviewed
• [Journal Article] Autologous CTL response against cancer stem-like cells/cancer-initiating cells of bone malignant fibrous histiocytoma (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Cytotoxic T lymphocytes efficiently recognize human colon cancer stem-like cells (2011)
  • 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
  • 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, Tamura Y, Kamiguchi K, Kutomi G, Sahara H, Torigoe T, Himi T, Sato N
  • Journal Title: Int Immunol Volume: 23(4) Pages: 223-37
  • 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(2) Pages: 93-102
  • 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, 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
  • 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(7) Pages: 4325-30
  • 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
  • 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 cells (2011)
  • Author(s): Oura J, et al
  • Journal Title: Int.Immunol Volume: 23 Issue: 4 Pages: 223-237
  • DOI: 10.1093/intimm/dxr013
  • Peer Reviewed
• [Journal Article] The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma (2011)
  • 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
  • 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
  • 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., 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
  • Peer Reviewed
• [Journal Article] Tumor associated dendritic cells : molecular mechanisms to suppress anti-tumor immunity (2011)
  • Author(s): Hirohashi, Y. and Sato, N.
  • Journal Title: Immunotherapy Volume: 3 Issue: 8 Pages: 945-947
  • DOI: 10.2217/imt.11.94
  • Peer Reviewed
• [Journal Article] Phase I clinical trial of survivin-derived peptide vaccine therapy for patients with advanced or recurrent oral cancer (2011)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Autoantibody against hypoxia-inducible factor prolyl hydroxylase-3 is a potential serological marker for renal cell carcinoma (2011)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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
• [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