2002 年度実績報告書

ヒトCD8+キラーT細胞により認識されるがん拒絶抗原の解析

研究課題

研究課題/領域番号	12213134
研究機関	久留米大学
研究代表者	伊東恭悟久留米大学, 医学部, 教授 (50125499)
キーワード	遺伝子 / 拒絶抗原 / ペプチド / 免疫 / キラーT細胞 / ワクチン / 探索的臨床研究 / テーラーメイド型医療
研究概要	1)HLA-A2拘束性癌関連抗原をコードする遺伝子を新規に2つクローニングし、そのペプチド4種類をワクチン候補として決定。さらに新規CTLエピトープペプチドとしてEZH-2及びPSCA由来ペプチドを同定した。 2)HLA-A24拘束性癌関連抗原をコードする遺伝子を4種類新規クローニングし、そのペプチド7種類をワクチン候補として決定した。さらにテーラーメイドペプチドワクチン治療に向けて腫瘍マーカーや癌の分子標的分子由来のCTLエピトープペプチドを多数同定した(Her 2/neu, CEA, EGF-R及びEZH-2など)。これらは全て平成15年度開始の早期第I相臨床試験に使用予定(再燃前立腺癌、スキルス胃癌、子宮頸癌、大腸癌、乳癌、肺癌、肝癌)。 3)HLA-A26拘束性癌関連抗原をコードする遺伝子を2種類(エピトープペプチドは2個)同定した。 4)HLA-A31拘束性癌関連抗原をコードする遺伝子を2種類(エピトープペプチドは3種類)同定した。 5)HLA-B46及びB52関連抗原をコードする遺伝子を各々2及び3種類クローニングし、かつ複数のエピトープペプチドも同定した。 6)ペプチド特異的CTL同定法の高速・高感度法を確立した。これによりテーラーメイド型ペプチドワクチンが可能となり、また正確なモニタリングも可能となった。以上の研究成果は(平成14年度)は英文業績誌19編(Can. Res.2編を含む)に掲載された。また知的所有権3件申請(6件申請準備中)された。

研究成果
(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Sasatomi T, Itoh K., et al.: "Expression of Tumor Rejection Antigens in Colorectal Carcinomas"Cancer. 94. 1636-1641 (2002)
[文献書誌] Suzuki N., Itou K., et al.: "Detection of peptide-specific Cytotoxic T lymphocyte precursors used for specific immunotherapy of pancreatic cancer"Int. J. Cancer. 98. 45-50 (2002)
[文献書誌] Tanaka K., Itoh K., et al.: "Serine proteinase inhibitor 9 can be recognized by cytotoxic T lymphocytes of epithelial cancer patients"Jpn. J. Cancer Res.. 98. 198-208 (2002)
[文献書誌] Yutani S., Itoh K., et al.: "Elevation of serum MAGE-4 protein levels and prediction of hepatocellular carcinogenesis in patients with liver cirrhosis"Jpn. J. Cancer Res.. 93. 453-458 (2002)
[文献書誌] Nakatsura R., Itoh K., et al.: "Cellular and humoral immune responses to a human pancreatic cancer antigen, CLP, originally defined by the SEREX method"Eur. J. Immunology. 32. 826-836 (2002)
[文献書誌] Hida N., Itoh K., et al.: "A simple culture protocol to detect peptide-specific cytotoxic T lymphocyte precursors in the circulation"Cancer Immunol. Immunother.. 51. 219-228 (2002)
[文献書誌] Komatsu N., Itoh K., et al.: "Measurement of interferon-γ by high-throughput fluorometric microvolume assay technology system"J. Immunological Methods. 263. 169-176 (2002)
[文献書誌] Ohkouchi S., Itoh K., et al.: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of healthy individuals"Tissue Antigens. 59. 259-272 (2002)
[文献書誌] Maeda Y., Itoh K., et al.: "Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2-restriceted and tumor-specific CTLs in the majority of gastrointestinal cancer patients"Int. J. Cancer. 99. 409-417 (2002)
[文献書誌] Gohara R., Itoh K., et al.: "Phase I Clinical Study of Cyclophilin B Peptide Vaccine for patients with Lung Cancer"J. Immuotherapy. 25. 439-444 (2002)
[文献書誌] Maeda Y., Itoh K., et al.: "Detection of peptide-specific CTL-precursors in peripheral blood lymphocytes of cancer patients"Br. J. Cancer. 87. 796-804 (2002)
[文献書誌] Nonaka Y., Itoh K., et al.: "Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes form patients with brain tumors"Tissue Antigen. 60. 319-327 (2002)
[文献書誌] Tsuda N., Itoh K., et al.: "UDP-Gal: β GlcNAc β1,3-galactosyltransferase, polypeptide 3 (GALT3) is a tumor antigen recognized by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumor"Br. J. Cancer. 87. 1006-1012 (2002)
[文献書誌] Azuma K., Itoh K., et al.: "Mutated p53 gene encodes a non-mutated epitope recognized by HLA-B4601-restritced and tumor-reactive CTLs at tumor site"Tissue Antigens. 63. 854-858 (2003)
[文献書誌] Koga M., Itoh K., et al.: "Identification of ribosomal proteins S2 and L10a as tumor antigensrecognized by HLA-A26-restricted CTL"Tissue Antigens. (in press). (2003)
[文献書誌] Yamada A., Itoh K., et al.: "Gene and peptide analyses of newly defined lung cancer rejection antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes"Cancer Res.. (in press). (2003)
[文献書誌] Noguchi M., Itho K., et al.: "Induction of cellular and humoral immune responses to tumor cells and peptide in hla-A24 positive hormone-refractory prostate cancer patients by peptide vaccination"The Prostate. (in press). (2003)
[文献書誌] Kawamoto N., Itoh K., et al.: "IgG reactive to CTL-directed epitopes of self-antigens is eitherr lacking or unbalanced in atopic dermatitis patients"Tissue Antigen. (in press). (2003)
[文献書誌] Kyogo Itoh: "Tumor Immunology Series volume III"Drs. kawakami and Parmiani (harwood academic publishers)(In press). (2003)

2002 年度 実績報告書

ヒトCD8+キラーT細胞により認識されるがん拒絶抗原の解析

研究代表者

伊東 恭悟 久留米大学, 医学部, 教授 (50125499)

研究成果

[文献書誌] Sasatomi T, Itoh K., et al.: "Expression of Tumor Rejection Antigens in Colorectal Carcinomas"Cancer. 94. 1636-1641 (2002)

[文献書誌] Suzuki N., Itou K., et al.: "Detection of peptide-specific Cytotoxic T lymphocyte precursors used for specific immunotherapy of pancreatic cancer"Int. J. Cancer. 98. 45-50 (2002)

[文献書誌] Tanaka K., Itoh K., et al.: "Serine proteinase inhibitor 9 can be recognized by cytotoxic T lymphocytes of epithelial cancer patients"Jpn. J. Cancer Res.. 98. 198-208 (2002)

[文献書誌] Yutani S., Itoh K., et al.: "Elevation of serum MAGE-4 protein levels and prediction of hepatocellular carcinogenesis in patients with liver cirrhosis"Jpn. J. Cancer Res.. 93. 453-458 (2002)

[文献書誌] Nakatsura R., Itoh K., et al.: "Cellular and humoral immune responses to a human pancreatic cancer antigen, CLP, originally defined by the SEREX method"Eur. J. Immunology. 32. 826-836 (2002)

[文献書誌] Hida N., Itoh K., et al.: "A simple culture protocol to detect peptide-specific cytotoxic T lymphocyte precursors in the circulation"Cancer Immunol. Immunother.. 51. 219-228 (2002)

[文献書誌] Komatsu N., Itoh K., et al.: "Measurement of interferon-γ by high-throughput fluorometric microvolume assay technology system"J. Immunological Methods. 263. 169-176 (2002)

[文献書誌] Ohkouchi S., Itoh K., et al.: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of healthy individuals"Tissue Antigens. 59. 259-272 (2002)

[文献書誌] Maeda Y., Itoh K., et al.: "Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2-restriceted and tumor-specific CTLs in the majority of gastrointestinal cancer patients"Int. J. Cancer. 99. 409-417 (2002)

[文献書誌] Gohara R., Itoh K., et al.: "Phase I Clinical Study of Cyclophilin B Peptide Vaccine for patients with Lung Cancer"J. Immuotherapy. 25. 439-444 (2002)

[文献書誌] Maeda Y., Itoh K., et al.: "Detection of peptide-specific CTL-precursors in peripheral blood lymphocytes of cancer patients"Br. J. Cancer. 87. 796-804 (2002)

[文献書誌] Nonaka Y., Itoh K., et al.: "Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes form patients with brain tumors"Tissue Antigen. 60. 319-327 (2002)

[文献書誌] Tsuda N., Itoh K., et al.: "UDP-Gal: β GlcNAc β1,3-galactosyltransferase, polypeptide 3 (GALT3) is a tumor antigen recognized by HLA-A2-restricted cytotoxic T lymphocytes from patients with brain tumor"Br. J. Cancer. 87. 1006-1012 (2002)

[文献書誌] Azuma K., Itoh K., et al.: "Mutated p53 gene encodes a non-mutated epitope recognized by HLA-B4601-restritced and tumor-reactive CTLs at tumor site"Tissue Antigens. 63. 854-858 (2003)

[文献書誌] Koga M., Itoh K., et al.: "Identification of ribosomal proteins S2 and L10a as tumor antigensrecognized by HLA-A26-restricted CTL"Tissue Antigens. (in press). (2003)

[文献書誌] Yamada A., Itoh K., et al.: "Gene and peptide analyses of newly defined lung cancer rejection antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes"Cancer Res.. (in press). (2003)

[文献書誌] Noguchi M., Itho K., et al.: "Induction of cellular and humoral immune responses to tumor cells and peptide in hla-A24 positive hormone-refractory prostate cancer patients by peptide vaccination"The Prostate. (in press). (2003)

[文献書誌] Kawamoto N., Itoh K., et al.: "IgG reactive to CTL-directed epitopes of self-antigens is eitherr lacking or unbalanced in atopic dermatitis patients"Tissue Antigen. (in press). (2003)

[文献書誌] Kyogo Itoh: "Tumor Immunology Series volume III"Drs. kawakami and Parmiani (harwood academic publishers)(In press). (2003)

2002 年度実績報告書

伊東恭悟久留米大学, 医学部, 教授 (50125499)