2003 年度実績報告書

大腸癌組織浸潤リンパ球が認識する抗原群のクローニングと解析

研究課題

研究課題/領域番号	14570526
研究機関	久留米大学
研究代表者	七條茂樹久留米大学, 医学部, 助教授 (30080592)
キーワード	腫瘍浸潤リンパ球 / 細胞傷害性T細胞 / cDNA / タンパク質 / ペプチド / 細胞増殖 / RT-PCR / HLA-A2結合モチーフ
研究概要	【目的】腫瘍浸潤リンパ球(TIL)由来の細胞傷害性T細胞(CTL)株が認識する分子群が機能分類上どの様な分子種を認識しているのかを探索する。【実験成績および考察】大腸癌TILから樹立したOK-CTL株が認識する遺伝子群74種類を単離・解析した。その結果、(a)重複遺伝子6種類、断片遺伝子41種類で、既知タンパク質もしくはその断片、あるいは機能モチーフを有する未知遺伝子27種類を選別した。(b)TILが特異的に認識する事が証明されたペプチドをコードする遺伝子の機能を各種データベース検索による推定し、免疫系が生体で認識している自己抗原の機能別分類を行ったところ、細胞増殖に関与または増殖の結果発現が亢進および分子の運搬に関与する分子が多いことがわかった。(c)上記遺伝子がコードするタンパク質のアミノ酸配列から、HLA-A2結合モチーフを持った9-10残基のオリゴペプチド配列を393種類委託合成し、HLA-A2をもったT2細胞株にペプチドを感作して標的細胞としてOK-CTLがペプチドの濃度依存性に認識した68種類のペプチドを選別した。(d)68種類のペプチドのうち、26種類は、IL2で増殖させた患者末梢血リンパ球により認識されることが確認された。(e)そのうちの16種類は、試験管内での患者末梢血からのCTL誘導能が確認された。(f)27種類のうちHLA-B46拘束性に2種類、HLA-A31拘束性に4種類の遺伝子産物が認識され、またこれらの遺伝子産物がコードするCTL誘導能を有するペプチドをそれぞれ5種類および7種類同定した。【結語】TIL由来のCTL株が認識する分子群は、細胞増殖に関与または増殖の結果発現が亢進する自己抗原遺伝子が多く、次に分子の運搬に関与する分子が多いことがわかった。

研究成果

(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] Sasada T: "Analysis of cellular localization of SART3 tumor antigen by a newly established monoclonal antibody : Heterotopic expression of SART3 on the surface of B-lineage leukemic cells."Cancer Res.. in press. (2004)
[文献書誌] Koga M: "Analysis of cellular localization of SART3 tumor antigen by a newly established monoclonal antibody : Heterotopic expression of SART3 on the surface of B-lineage leukemic cells."Oncol.Rep.. 11(4). 785-789 (2004)
[文献書誌] Azuma K: "Identification of HER2/neu-derived peptides capable of inducing both cellular and humoral immune responces in HLA-A24 positive breast cancer patients"Breast Cancer Res.Treat.. in press. (2004)
[文献書誌] Takedatsu H: "Identification of peptide vaccine candidates sharing among HLA-A3^+, -All^+, -A31^+, and -A33^+~ cancer patients."Clin.Cancer Res.. 10(3). 1112-1120 (2004)
[文献書誌] Ishihara Y: "HER2/neu-derived peptides recognized by both cellular and humoral immune system in HLA-A2+ cancer patients."Int.J.Oncol.. 24(4). 967-975 (2004)
[文献書誌] Shomura H: "Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2^+ cancer patients."Br.J.Cancer.. in press. (2004)
[文献書誌] Mine T: "Humoral responses to peptides correlate with overall survival in advanced cancer patients vaccinated with peptides based on pre-existing peptide-specific cellular responses."Clin.Cancer Res.. 10(3). 929-937 (2004)
[文献書誌] Takedatsu H: "Detection of a set of peptide vaccine candidates for use in HLA-A31^+ epithelial cancer patients."Int.J.Oncol.. 24(2). 337-347 (2003)
[文献書誌] Ohkouchi S: "Identification of a CTL-directed epitope encoded Testin of the common fragile site 7G region : a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients."Eur.J.Immunol.. 33(11). 2964-2973 (2003)
[文献書誌] Shichijo S: "Identification of two novel tumor-associated antigens recognized by HLA-B46-restricted cytotoxic T lymphocytes."Int.J.Mol.Med.. 12(6). 895-902 (2003)
[文献書誌] Azuma K: "Heat shock cognate protein 70 encodes antigenic epitopes recognized by HLA-B4601-restricted cvtotoxic T lymphocytes from cancer patients."Br.J.Cancer.. 89(6). 1079-1085 (2003)
[文献書誌] Kawamoto N: "IgG reactive to CTL-directed epitopes of self-antigens is enter lacking or unbalanced in atopic dermatitis patients."Tissue Antigen.. 61(5). 352-361 (2003)
[文献書誌] Azuma K: "Mutated p53 gene encodes a non-mutated epitope recognized by HLA-B^*4601-restricted and tumor cell-reactive CTLs at tumor site."Cancer Res.. 63(4). 854-858 (2003)
[文献書誌] Koga M: "Identification of ribosomal proteins S2 and L10a as tumor-rejection antigens recognized by HLA-A26 restricted CTL."Tissue Antigen.. 61(2). 136-145 (2003)
[文献書誌] Nonaka Y: "Recognition of ADP-ribosylation factor by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients with brain tumors."Tissue Antigen.. 60(4). 319-327 (2002)
[文献書誌] Tsuda N: "UDP-Gal : βGlcNAcb1, 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(9). 1006-1012 (2002)
[文献書誌] Maeda Y: "Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2 restricted and tumor-specific CTLs in the majority of gastrointestinal cancer patients."Int.J.Cancer.. 99(3). 409-417 (2002)
[文献書誌] Ohkouchi S: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of health individuals."Tissue Antigen.. 59(4). 259-272 (2002)
[文献書誌] Komatsu N: "Measurement of interferon-g by high-throughput fluorometric microvolume assay technology (FMAT) system."J.Immunol.Method.. 263(1-2). 169-176 (2002)
[文献書誌] Yutani S: "Elevation of serum MAGE-4 protein levels and prediction of hepatocellular carcinogenesis in patients with liver cirrhosis"Jpn.J.Cancer Res.. 93(4). 453-458 (2002)
[文献書誌] Tanaka K: "Serine proteinase inhibitor 9 can be recognized by cytotoxic T lymphocytes of epithelial cancer patients."Jpn.J.Cancer Res.. 93(2). 198-208 (2002)

2003 年度 実績報告書

大腸癌組織浸潤リンパ球が認識する抗原群のクローニングと解析

研究代表者

七條 茂樹 久留米大学, 医学部, 助教授 (30080592)

研究成果

[文献書誌] Sasada T: "Analysis of cellular localization of SART3 tumor antigen by a newly established monoclonal antibody : Heterotopic expression of SART3 on the surface of B-lineage leukemic cells."Cancer Res.. in press. (2004)

[文献書誌] Koga M: "Analysis of cellular localization of SART3 tumor antigen by a newly established monoclonal antibody : Heterotopic expression of SART3 on the surface of B-lineage leukemic cells."Oncol.Rep.. 11(4). 785-789 (2004)

[文献書誌] Azuma K: "Identification of HER2/neu-derived peptides capable of inducing both cellular and humoral immune responces in HLA-A24 positive breast cancer patients"Breast Cancer Res.Treat.. in press. (2004)

[文献書誌] Takedatsu H: "Identification of peptide vaccine candidates sharing among HLA-A3^+, -All^+, -A31^+, and -A33^+~ cancer patients."Clin.Cancer Res.. 10(3). 1112-1120 (2004)

[文献書誌] Ishihara Y: "HER2/neu-derived peptides recognized by both cellular and humoral immune system in HLA-A2+ cancer patients."Int.J.Oncol.. 24(4). 967-975 (2004)

[文献書誌] Shomura H: "Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2^+ cancer patients."Br.J.Cancer.. in press. (2004)

[文献書誌] Mine T: "Humoral responses to peptides correlate with overall survival in advanced cancer patients vaccinated with peptides based on pre-existing peptide-specific cellular responses."Clin.Cancer Res.. 10(3). 929-937 (2004)

[文献書誌] Takedatsu H: "Detection of a set of peptide vaccine candidates for use in HLA-A31^+ epithelial cancer patients."Int.J.Oncol.. 24(2). 337-347 (2003)

[文献書誌] Ohkouchi S: "Identification of a CTL-directed epitope encoded Testin of the common fragile site 7G region : a peptide vaccine candidate for HLA-B52+ and HLA-62+ cancer patients."Eur.J.Immunol.. 33(11). 2964-2973 (2003)

[文献書誌] Shichijo S: "Identification of two novel tumor-associated antigens recognized by HLA-B46-restricted cytotoxic T lymphocytes."Int.J.Mol.Med.. 12(6). 895-902 (2003)

[文献書誌] Azuma K: "Heat shock cognate protein 70 encodes antigenic epitopes recognized by HLA-B4601-restricted cvtotoxic T lymphocytes from cancer patients."Br.J.Cancer.. 89(6). 1079-1085 (2003)

[文献書誌] Kawamoto N: "IgG reactive to CTL-directed epitopes of self-antigens is enter lacking or unbalanced in atopic dermatitis patients."Tissue Antigen.. 61(5). 352-361 (2003)

[文献書誌] Azuma K: "Mutated p53 gene encodes a non-mutated epitope recognized by HLA-B^*4601-restricted and tumor cell-reactive CTLs at tumor site."Cancer Res.. 63(4). 854-858 (2003)

[文献書誌] Koga M: "Identification of ribosomal proteins S2 and L10a as tumor-rejection antigens recognized by HLA-A26 restricted CTL."Tissue Antigen.. 61(2). 136-145 (2003)

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

[文献書誌] Tsuda N: "UDP-Gal : βGlcNAcb1, 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(9). 1006-1012 (2002)

[文献書誌] Maeda Y: "Cleavage and polyadenylation specificity factor (CPSF)-derived peptides can induce HLA-A2 restricted and tumor-specific CTLs in the majority of gastrointestinal cancer patients."Int.J.Cancer.. 99(3). 409-417 (2002)

[文献書誌] Ohkouchi S: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of health individuals."Tissue Antigen.. 59(4). 259-272 (2002)

[文献書誌] Komatsu N: "Measurement of interferon-g by high-throughput fluorometric microvolume assay technology (FMAT) system."J.Immunol.Method.. 263(1-2). 169-176 (2002)

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

[文献書誌] Tanaka K: "Serine proteinase inhibitor 9 can be recognized by cytotoxic T lymphocytes of epithelial cancer patients."Jpn.J.Cancer Res.. 93(2). 198-208 (2002)

2003 年度実績報告書

七條茂樹久留米大学, 医学部, 助教授 (30080592)