2003 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	新規ペプチド同定は、32種類をワクチン候補として同定した(知的所有権5件申請済み,4件申請予定)。現在、それらを第I相・早期第II相臨床試験にGMPレベルのペプチドとして使用中である。一方、HLA-A24と-A2以外HLA-クラスIアレールに拘束されるヒト癌拒絶抗原遺伝子とそのペプチド分子の同定も継続して実施中であり、平成15年度は多数のHLA-A26、-A31、-B46及び-B52拘束性遺伝子群とペプチドを同定した。これまでの我々の研究は基礎レベルから癌ペプチドワクチン第I相臨床試験へと展開され、現在早期第II相臨床試験がスキルス胃癌、大腸癌、再燃前立腺癌、子宮頸癌、悪性脳腫瘍等においては進行中であり、今後のペプチドワクチン臨床応用への道を開拓する研究と評価される。 (1)HLA-A24拘束性新規肺癌遺伝子とペプチドを同定した(Yamada et al.,Can.Res.,2003). (2)ワクチン候補ペプチドをコードする新規ペプチドを更に32種類同定し全体で66種類にて臨床試験可能とした。腫瘍マーカー由来(HER2/neu, EGFR, PSA, PAP, PSMA, PSCN, CEA, PTHrp, EZH2)である、 (3)HLA-A3スーパーファミリーに拘束されるペプチドを5種類同定した(Takedatsu et al.,Clin Can Res,2004)その結果、ほぼ全例へのペプチドワクチンを可能となった(HLA多型性は-A24、-A2及び-A3ファミリーでほぼ100%カバー可能)。 (4)HLA-B46、-B52、-B60拘束性遺伝子およびペプチドを同定した(Azuma et al., Can Res.2003)。 (5)(4)ペプチドに対するCD4陽性ヘルパーT細胞反応を解明した(Harada et al.J.Immunol.2004)。 (6)HLA-31拘束性新規遺伝子とペプチドを同定した(Sasada et al. Can。Res.2004) 以上の研究成果は、英文査読誌(33編)に発表済みもしくは予定であり、知的所有権は12件を申請した。

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] Kobayashi K., Itoh K, et al.: "Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prost cancer patients."Cancer Sci. 94. 622-627 (2003)
[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."Cancer Res.. 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. 61. 136-145 (2003)
[文献書誌] Yamada A., Itoh K, et al.: "Gene and peptide analyses of newly defined lung cancer rejection antigens reconized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes."Cancer Res.. 63. 2829-2835 (2003)
[文献書誌] Noguchi M., Itoh 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. 57. 80-92 (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. 62. 352-361 (2003)
[文献書誌] Azuma K., Itoh K., et al.: "Heat shock cognate protein 70 encodes antigenic epitopes recognised by HLA-B4601-restricted cytotoxic T lymphocytes from cancer patients."Br.J.Cancer. 89. 1079-1085 (2003)
[文献書誌] Harada M., Itoh K., et al.: "Target molecules in specific immunotherapy against prostate cancer."Int.J.Clin.Oncol. 8. 193-199 (2003)
[文献書誌] Mine T., Itoh K., et al.: "Immunological evaluation of CTL precursor-oriented vaccines for advand lung cancer patients."Cancer Sci.. 94. 548-556 (2003)
[文献書誌] Sato Y., Itoh K., et al.: "Immunological evaluation of peptide vaccination for patients with gast cancer based on pre-existing cellular response to peptide."Cancer Sci.. 94. 802-808 (2003)
[文献書誌] Shichijo S., Itoh K., et al.: "Identification of two novel tumor-associated antigens recognized HLA-B46-restricted cytotoxic T lymphocytes."Int.J.Mol.Med.. 12. 895-902 (2003)
[文献書誌] Ohkouchi S., Itoh K., et al.: "Identification of a CTL-directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region : a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients."Eur.J.Immunol. 33. 2964-2973 (2003)
[文献書誌] Tanaka S., Itoh K, et al.: "Peptide vaccination for patients with melanoma and other types of cancer bas on pre-existing peptide-specific cytotoxic T-lymphocyte precursors in the periphery."J.Immunother.. 26. 357-366 (2003)
[文献書誌] Harada M., Itoh K, et al.: "Prostate-specific antigen-derived epitopes capable of inducing cellular and humoral responses in HLA-A24+ prostate cancer patients"The prostate. 57. 152-159 (2003)
[文献書誌] Noguchi M., Itoh K, et al.: "Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer."Cancer Sci.. 95. 77-84 (2004)
[文献書誌] Takedatsu H., Itoh K, et al.: "Detection of a set of peptide vaccine candidates for use in HLA-A31+ epithelial cancer patients. International"Int.J.Oncol.. 24. 337-347 (2004)
[文献書誌] Tsuda N., Itoh K, et al.: "Vaccination with pre designated or evidence-based peptides for patients with recurrent gynecologic cancers."J Immunother. 27. 60-72 (2004)
[文献書誌] Harada M., Itoh K, et al.: "In vivo evidence that peptide vaccination can induce HLA-DR-restricted CD T cells reactive to a class I tumor peptides."J Immunol. 172. 2659-2667 (2004)
[文献書誌] Kyogo Itoh: "Tumor Immunology Series volume III"Drs.Kawakami and Parmiani (harwood academic publishers)(in press). (2004)

2003 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] Kobayashi K., Itoh K, et al.: "Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prost cancer patients."Cancer Sci. 94. 622-627 (2003)

[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."Cancer Res.. 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. 61. 136-145 (2003)

[文献書誌] Yamada A., Itoh K, et al.: "Gene and peptide analyses of newly defined lung cancer rejection antigens reconized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes."Cancer Res.. 63. 2829-2835 (2003)

[文献書誌] Noguchi M., Itoh 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. 57. 80-92 (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. 62. 352-361 (2003)

[文献書誌] Azuma K., Itoh K., et al.: "Heat shock cognate protein 70 encodes antigenic epitopes recognised by HLA-B4601-restricted cytotoxic T lymphocytes from cancer patients."Br.J.Cancer. 89. 1079-1085 (2003)

[文献書誌] Harada M., Itoh K., et al.: "Target molecules in specific immunotherapy against prostate cancer."Int.J.Clin.Oncol. 8. 193-199 (2003)

[文献書誌] Mine T., Itoh K., et al.: "Immunological evaluation of CTL precursor-oriented vaccines for advand lung cancer patients."Cancer Sci.. 94. 548-556 (2003)

[文献書誌] Sato Y., Itoh K., et al.: "Immunological evaluation of peptide vaccination for patients with gast cancer based on pre-existing cellular response to peptide."Cancer Sci.. 94. 802-808 (2003)

[文献書誌] Shichijo S., Itoh K., et al.: "Identification of two novel tumor-associated antigens recognized HLA-B46-restricted cytotoxic T lymphocytes."Int.J.Mol.Med.. 12. 895-902 (2003)

[文献書誌] Ohkouchi S., Itoh K., et al.: "Identification of a CTL-directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region : a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients."Eur.J.Immunol. 33. 2964-2973 (2003)

[文献書誌] Tanaka S., Itoh K, et al.: "Peptide vaccination for patients with melanoma and other types of cancer bas on pre-existing peptide-specific cytotoxic T-lymphocyte precursors in the periphery."J.Immunother.. 26. 357-366 (2003)

[文献書誌] Harada M., Itoh K, et al.: "Prostate-specific antigen-derived epitopes capable of inducing cellular and humoral responses in HLA-A24+ prostate cancer patients"The prostate. 57. 152-159 (2003)

[文献書誌] Noguchi M., Itoh K, et al.: "Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer."Cancer Sci.. 95. 77-84 (2004)

[文献書誌] Takedatsu H., Itoh K, et al.: "Detection of a set of peptide vaccine candidates for use in HLA-A31+ epithelial cancer patients. International"Int.J.Oncol.. 24. 337-347 (2004)

[文献書誌] Tsuda N., Itoh K, et al.: "Vaccination with pre designated or evidence-based peptides for patients with recurrent gynecologic cancers."J Immunother. 27. 60-72 (2004)

[文献書誌] Harada M., Itoh K, et al.: "In vivo evidence that peptide vaccination can induce HLA-DR-restricted CD T cells reactive to a class I tumor peptides."J Immunol. 172. 2659-2667 (2004)

[文献書誌] Kyogo Itoh: "Tumor Immunology Series volume III"Drs.Kawakami and Parmiani (harwood academic publishers)(in press). (2004)

2003 年度実績報告書

伊東恭悟久留米大学, 医学部, 教授 (50125499)