Human cancer vaccines

• Project/Area Number: 12213116
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Sapporo Medical University
• Principal Investigator: SATO Noriyuki Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (50158937)
• Co-Investigator(Kenkyū-buntansha): 田村 保明 札幌医科大学, 医学部, 助手 (80322329) ; 佐原 弘益 札幌医科大学, 臨海研究所, 助手 (10260762)
• Project Period (FY): 2000 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥50,300,000 (Direct Cost: ¥50,300,000); Fiscal Year 2004: ¥10,500,000 (Direct Cost: ¥10,500,000); Fiscal Year 2003: ¥10,700,000 (Direct Cost: ¥10,700,000); Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2001: ¥10,100,000 (Direct Cost: ¥10,100,000); Fiscal Year 2000: ¥8,000,000 (Direct Cost: ¥8,000,000)
• Keywords: tumor antigens / peptide vaccines / CTL / clinical trials / autologous tumor / Bioinformatics / survivin / SYT-SSX / 癌ワクチン / 癌抗原ペプチド / 胃癌抗原遺伝子 / 骨肉腫抗原遺伝子 / HLA-A24 / PBF / 肉腫 / 臨床試験 / 癌免疫 / 癌抗原処理提示 / 抗原ペプチド / hsc 70 / 分子シャペロン / ヒト癌抗原 / リカバリン / HLA-DR8

Research Abstract

Three research projects were successfully studied. 1) We identified human osteosarcoma antigen PBF, papilloma-binding factor, from autologous CTL and osteosarcoma OS2000 line. PBF was expressed in a large part of soft part tumors as well as approximately 50 % tumors of epithelial origins, whereas it was not detected in normal part of tissues particularly in the protein level. These observations suggest that PBF could be utilized in the immunotherapy of cancers. 2) Reverse-immunological approaches of tumor antigens indicated that survivin could work as the tumor antigens. Particularly, survivin-derived 2Bpeptide induced CTL in many cancer patients in the HLA-A24 restricted manner. We are now underway the phase I clinical trials of this peptide in colon, breast, lung cancers, indicating that there are no adverse effects. Some of these patients demonstrated certain clinical responses such as reduction in tumor size in CT as well as in tumor marker levels. We are also underway the phase I clinical trials of HLA-A24-restricted B peptide derived from the SYT-SSX chromosomal translocation fusion product in synovial sarcoma patients. In this trial, there are no adverse effects, and two out of six patients indicated an increasing number of tetramer-positive CTL precursors. 3) We identified 35 novel tumor antigens by bioinformatics in silico approaches. Wet studies by using RT-PCR analysis confirmed that 7 out of 35 antigens have strict expression profiles as the tumor antigens.

Research Products

• [Journal Article] Aberrant expression and potency as a cancer immunotherapy target of IAP family, Livin/ML-IAP in Lung Cancer. (2005)
  • Author(s): Hariu, H.
  • Journal Title: Clin.Cancer Res. 11 Pages: 1000-1009
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Aberrant expression and potency as a cancer immunotherapy target of IAP family, Livin/ML-IAP in Lung Cancer. (2005)
  • Author(s): Hariu, H., Hirohashi, Y., Torigoe, T., Tamura, Y., Aketa, K., Kitamura, H., Idenoue, S., Hariu, M., Kamiguchi, K., Mano, Y., Kanaseki, T., Tsukahara, T., Shijubo, N., Sato, N.
  • Journal Title: Clin.Cancer Res. 11 Pages: 1000-1009
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins. (2005)
  • Author(s): Idenoue, S., Hirohashi, Y., Torigoe, T., Sato, Y., Tamura, Y., Hariu, H., Yamamoto, M., Kurotaki, T., Tsuruma, T., Asanuma, H., Kanaseki, T., Ikeda, H., Kashiwagi, K., Okazaki, M., Sasaki, K., Sato, T., Ohmura, T., Hata, F., Yamaguchi, K., Hirata, K., Sato, N.
  • Journal Title: Clin.Cancer Res. 11 Pages: 1474-82
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A calcium binding protein, S100A4, mediates T cell dependent cytotoxicity as a transformation-associated antigen. (2005)
  • Author(s): Kondo, N., Ichimiya, S., Tamura, Y., Tonooka, A., Koshiba, S., Torigoe, T., Kamiguchi, K., Takenaga, K., Sato, N.
  • Journal Title: Microbiol.Immunol. 49 Pages: 49-56
  • NAID: 10014377175
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of human autologous cytotoxic T-lymphocyte-defined osteosarcoma gene that encodes a transcriptional regulator, papillomavirus binding factor. (2004)
  • Author(s): Tsukahara, T.
  • Journal Title: Cancer Res. 64 Pages: 5442-5448
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Tumor-derived heat shock protein70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymphocytes (CTLs) and tumor immunity. (2004)
  • Author(s): Ueda, G.
  • Journal Title: Cancer Science 95 Pages: 248-253
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. (2004)
  • Author(s): Tsuruma, T.
  • Journal Title: J.Translational Med. 2 Pages: 19-29
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A^*2402 anchor substitute. (2004)
  • Author(s): Ida, K.
  • Journal Title: J.Immunol. 173 Pages: 1436-1443
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Regulation of MHC class II expression in glioma cells by class II transactivator (C IITA). (2004)
  • Author(s): Takamura, Y.
  • Journal Title: Glia 45 Pages: 392-405
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of human autologous cytotoxic T-lymphocyte-defined osteosarcoma gene that encodes a transcriptional regulator, papillomavirus binding factor. (2004)
  • Author(s): Tsukahara, T., Nabeta, Y., Kawaguchi, S., Ikeda, H., Sato, Y., Shimozawa, K., Ida, K., Asanuma, H., Hirohashi, Y., Torigoe, T., Hiraga, H., Nagoya, S., Wada, T., Yamashita, T., Sato, N.
  • Journal Title: Cancer Res. 64 Pages: 5442-5448
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tumor- derived heat shock protein70-pulsed dendritic cells elicit tumor- specific cytotoxic T lymphocytes (CTLs) and tumor immunity. (2004)
  • Author(s): Ueda, G., Tamura, Y., Hirai, I., Kamigichi, K., Ichimiya, S., Torigoe, T., Hiratsuka, H., Sunakawa, H., Sato, N.
  • Journal Title: Cancer Science 95 Pages: 248-253
  • NAID: 10013721926
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer. (2004)
  • Author(s): Tsuruma, T., Hata, F., Torigoe, T., Furuhata, T., Idenoue, S., Kurotaki, T., Yamamoto, M., Yagihashi, A., Ohmura, T., Yamaguchi, K., Katsuramaki, T., Yasoshima, T., Sasaki, K., Mizushima, Y., Minamida, H., Kimura, H., Akiyama, M., Hirohashi, Y., Asanuma, H., Tamura, Y., Shimozawa, K., Sato, N., Hirata, K.
  • Journal Title: J.Translational Med. 2 Pages: 19-29
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Crisscross CTL induction by SYT-SSX junction peptide and its HLA-A^*2402 anchor substitute. (2004)
  • Author(s): Ida, K., Kawaguchi, S., Sato, Y., Tsukahara, T., Nabeta, Y., Sahara, H., Ikeda, H., Torigoe, T., Ichimiya, S., Kamiguchi, K., Wada, T., Nagoya, S., Hiraga, H., Kawai, A., Ishii, T., Araki, N., Myoui, A., Matsumoto, S., Ozaki, T., Yoshikawa, H., Yamashita, T., Sato, N.
  • Journal Title: J.Immunol. 173 Pages: 1436-1443
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Regulation of MHC class II expression in glioma cells by class II transactivator (C II TA). (2004)
  • Author(s): Takamura, Y., Ikeda, H., Kanaseki, T., Toyota, M., Tokino, T., Imai, K., Hokin, K., Sato, N.
  • Journal Title: Glia 45 Pages: 392-405
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Tumor-derived heat shock protein70-pulsed dendritic cells elicit tumor-specific cytotoxic T lymohocytes (CTLs) and tumor immunity. (2004)
  • Author(s): Ueda, G.
  • Journal Title: Cancer Science 95 Pages: 248-253
• [Journal Article] Heat shock proteins; Chaperoning of innate and adaptive immunities. (2003)
  • Author(s): Tamura, Y., Sato, N.
  • Journal Title: Jpn.J.Hyperthermic Oncology 19 Pages: 131-139
  • NAID: 10029675612
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Histone deacetylation, but not hypermethylation, modifies CIITA and MHC calss II gene expression in squamous cell carcinomas. (2003)
  • Author(s): Kanaseki, T., Ikeda, H., Takamura, Y., Toyota, M., Hirohashi, Y., Tokino, T., Himi, T., Sato, N.
  • Journal Title: J.Immunol. 170 Pages: 4980-4985
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Annual Review免疫2005;熱ショック蛋白質(HSP)-ペプチド複合体による新しいMHCクラスI抗原提示経路(佐藤昇志, 他編集) (2005)
  • Author(s): 田村保明, 佐藤昇志
  • Total Pages: 8
  • Publisher: 中外医学社
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Annual Review免疫2005;熱ショック蛋白質(HSP)-ペプチド複合体による新しいMHCクラスI抗原提示経路(佐藤昇志、他編集) (2005)
  • Author(s): 田村保明, 佐藤昇志
  • Total Pages: 8
  • Publisher: 中外医学社
• [Patent(Industrial Property Rights)] サバイビン由来HLA-A24結合性癌抗原ペプチド (2004)
  • Inventor(s): 佐藤 昇志 他 4名
  • Industrial Property Number: 2004-191478
  • Filing Date: 2004-01-30
  • Description: 「研究成果報告書概要(和文)」より
• [Patent(Industrial Property Rights)] サバイビン由来HLA-A24結合性癌抗原ペプチド (2004)
  • Inventor(s): 佐藤 昇志 他4名
  • Industrial Property Rights Holder: 佐藤 昇志 他4名
  • Industrial Property Number: 2004-191478
  • Filing Date: 2004-01-30
• [Patent(Industrial Property Rights)] SYT-SSX改変ペプチド (2002)
  • Inventor(s): 佐藤 昇志 他 7名
  • Industrial Property Number: 2002-350633
  • Filing Date: 2002-12-03
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ida, K., Sato, N., et al.: "Improved induction of synovial sarcoma-reactive CTLs by SYT-SSX junction peptide/HLA-A*2402 complex anchor substitution."J.Immunol.. in press.
• [Publications] Idenoue, S., Sato, N., et al.: "A potent immunogenic general cancer vaccine that targets survivin, an inhibitor of apoptosis proteins."Clin.Cancer Res.. in press.
• [Publications] Ueda, G., Tamura, Y., Sato, N., et al.: "Tumor-derived Heat Shock Protein70-pulsed Dendritic Cells Elicit Tumor-specific Cytotoxic T Lymphocytes (CTLs) and Tumor Immunity."Cancer Science. 95・3. 248-253 (2004)
• [Publications] Takamura, Y., Ikeda, H., Sato, N., et al.: "Regulation of MHC class II expression in glioma cells by class II transactivator (C II TA)."Glia. 45. 392-405 (2004)
• [Publications] Tamura, Y., Sato, N.: "Heat shock proteins ; Chaperoning of innate and adaptive immunities."Jpn.J.Hyperthermic Oncology. 19. 131-139 (2003)
• [Publications] Kanaseki, T., Sato, N., et al.: "Histone deacetylation, but not hypermethylation, modifies CIITA and MHC calss II gene expression in squamous cell carcinomas."J.Immunol.. 170. 4980-4985 (2003)
• [Publications] 佐藤百合子, 井田和功, 川口 哲, 佐藤昇志: "Annual Review 2003 染色体転座融合蛋白を標的とした癌治療"中外医学社. 6 (2002)
• [Publications] Sato, Y., et al.: "Detection and induction of cytotoxic T lymphocytes specific for STY-SSX-derived peptides in HLA-A24+ patients with synovial sarcoma"J. Immunol.. 169. 1611-1618 (2002)
• [Publications] Maeda, A., et al.: "Vaccination with recoverin, a cancer-associated retinopathy antigen, induces autoimmune retinal dysfunction and tumor cell regression in mice"Eur. J. Immunol.. 32. 2300-2307 (2002)
• [Publications] Hirohashi, Y., et al.: "An HLA-A24-restricted CTL epitope of a tumor asscoated protein, survivin"Clin. Cancer Res.. 8. 1731-1739 (2002)
• [Publications] Rong, S., et al.: "Frequent detection of anti-recoverin cytotoxic T-lymphocytes precursor in peripheral blood of cancer patients by using an HLA-A24-recoverin-tetramer"Cancer Immunol. Immunother.. 51. 282-290 (2002)
• [Publications] Kondo, H., et al.: "Natural antigenic peptides from squamous cell carcinoma recognized by autologous HLA-DR8-restricted CD4+ T cells"Jap. J. Cancer Res.. 93. 917-924 (2002)
• [Publications] Sahara, H., et al.: "A gene encoding human gastric signet ring cell carcinoma antigen recognized by HLA-A31-restricted cytotoxic T lymphocytes"J. Immunother.. 25. 235-242 (2002)
• [Publications] 佐藤 昇志他: "Annual Review 2002 免疫"中外医学社. 350 (2002)
• [Publications] Shigehara, K.et al.: "IL-12 and IL-18 are increased and stimulate IFN-g production in sarcoid lungs"J.Immunol.. 166. 642-649 (2001)
• [Publications] Kishi, A.et al: "The cell surface-expressed HSC70-like molecule preferentially reacts with rat T cell receptor d6 family"Immunogenetics. 53. 401-409 (2001)
• [Publications] Maeda, A.et al.: "Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin,cancer associated retinopathy antige,to achieve a clinical better prognosis in a paraneoplastic syndrome"Eur.J.Immunol.. 31. 563-572 (2001)
• [Publications] Sahara, H.et al.: "A gene encoding human gastric signete ring cell carcinoma antigen recognized by HLA-A-A31-restricted cytotoxic T lymphocytes"J.Immunother. (in press).
• [Publications] Rong, S.et al.: "Frequent detection of anti-recoverin cytotoxic T-lymphocytes precursor in peripheral blood of cancer patients by using an HLA-A24-recoverin-tetramer"Cancer Immunol.Immunother.. (in press).
• [Publications] Sato, Y.et al.: "Detection and induction of cytotoxic T lymphocytes specific for SYT-SSX-derived peptides in HLA-A24+patients with synovial sarcoma"J.Immunol.. (in press).
• [Publications] 分担執筆;佐藤昇志: "Annual Review免疫2002"中外医学社. 310 (2002)
• [Publications] Maeda,A.,Ohguro,H.,Maeda,T.,Wada.T.,Sato,N.,Kuroki,Y. and Nakagawa,T.: "Aberrant expression of photoreceptor specific calcium binding protein (recoverin) in cancer cell lines."Cancer Res.. 60. 1914-1920 (2000)
• [Publications] Maeda,A.,Ohguro,H.,Nabeta,Y.,Nishimura,Y.,Kuroki,Y.,Sato,N. et al.: "Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, cancer associated retinopathy antige, to achieve a clinical better prognosis in a paraneoplastic syndrome."Eur.J.Immunol.. 31. 563-572 (2001)
• [Publications] Matsuura,A.,Kinebuchi,M.,Chen,H.Z,Kikuchi,K,Sato,N. et al.: "NK T cells in the rat : organ-specific distribution on NK T cells expressing distinct Va14 chains."J.Immunol.. 164. 3140-3148 (2000)
• [Publications] Nabeta,Y.,Sahara,H.,Suzuki,K.,WadaT.,Kikuchi,K.,Sato,N. et al.: "Induction of CTL from peripheralblood of HLA-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma."Jap.J.Cancer. 91. 616-621 (2000)
• [Publications] Shigehara,K.,Shujubo,N.,Ohmichi,M.,Abe,S.,Sato,N. et al.: "IL-12 and IL-18 are increased and stimulate IFN-γ production in sarcoid lungs."J.Immunol.. 166. 642-649 (2001)
• [Publications] Kamiguchi,K.,Torigoe,T.,Fujiwara,O.,Hirohashi,Y.,Sahara,H.,Hiraii,I.,Sato.N.: "73kD heat shock cognate protein in associated with transporters associated with antigen processing (TAP) and involved in feeding of MHC class I-presentable antigenic peptides to TAP."J.Immunol.. (in press).
• [Publications] Sato,N.,Nabeta,Y.,Kondo,H.,Sahara,H.,Takahashi,S.,Torigoe,T. et al.: "Cancer Chemother.Pharmacol."Human CD8 and CD4T cell epitope of epithelial cancer antigens.. 4 (2000)
• [Publications] 佐藤昇志,矢田純一,奥村康: "中外医学社"Annual Review免疫2000. 354 (2000)