2003 Fiscal Year Annual Research Report

新規肺癌抗原の同定とそれらを分子標的としたペプチドワクチンの開発

Research Project

Project/Area Number	15590834
Research Institution	Kurume University
Principal Investigator	山田亮久留米大学, 先端癌治療研究センター, 教授 (50158177)
Keywords	肺癌 / 癌免疫療法 / 癌抗原 / 癌ワクチン / ペプチドワクチン / 細胞傷害性T / 腫瘍免疫
Research Abstract	癌拒絶抗原の遺伝子クローニングと細胞傷害性Tリンパ域(CTL)によりHLA拘束性に認識される抗原ペプチドの同定を実施した。その結果、以下に示す6遺伝子によってコードされる癌抗原を同定することができた。これらのうちの1分子は全く新規にクローニングされたものであった。さらにこれらの分子に由来し、CTLによりHLA拘束性に認識される抗原ペプチド10分子を同定した。1)肺癌のcDNAライブラリーより新規癌拒絶抗原として3分子同定した(BTB domain containing 2,hairpin-binding Protein, clone 83)。これらのうち、clone 83は新規遺伝子であった。これらの遺伝子のコードするHLA-A24拘束性ペプチドも4種同定した。これらの遺伝子発現に着いても詳細に検討した。2)脳腫瘍cDNAライブラリーよりUDP-Gal:βGlcNAc β1,3-galactosyltransferase, polypeptide 3(GALT3)を同定した。この分子はHLA-A2拘束性にCTL認識される癌拒絶抗原である。GALT3のコードする抗原ペプチド3種を同定した。また、遺伝子発現を調べた結果、脳腫瘍以外にも肺癌をはじめとする種々の癌に広汎に発現していた。3)食道癌のcDNAライブラリーよりRibosomal proteins S2およびL10aを同定した。この分子はHLA-A26拘束性にCTLにより認識される癌拒絶抗原である。さらに、これらの遺伝子のコードするHLA-A26拘束性ペプチド3種も同定した。これらの分子は肺癌を含む種々の癌細胞にubiquitousに発現しているものであった。これらにより日本人の約9割の患者のHLAタイプに対応できる癌ワクチンが開発される事になる。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] M.Koga, N.Komatsu, S.Shichijo, K.Itoh, A.Yamada: "Analysis of cellular localization of SART3 tumor antigen by newly established monoclonal antibody : Heterotopic expression of SART3 tumor antigen on the surface of B-lineage leukemic cells."Oncol.Reports. in press. (2004)
[Publications] Y.Sato, Y.Maeda, T.Sasatomi, M.Takahashi, Y.Une, M.Kondo, T.Shinohara, N.Hida, K.Katagiri, K.Sato, A.Yamada, H.Yamana, K.Itoh, S.Todo: "A phase I trial of CTL-purecursor-oriented peptide vaccine for colorectal carcinoma patients."Br.J.Cancer. in press. (2004)
[Publications] M.Noguchi, K.Itoh, S.Suekane, A.Yao, N.Suetsugu, K.Katagiri, A.Yamada, H.Yamana, S.Noda: "Phase I trial of patient-oriented vaccination in HLA-A2 positive patients with metastatic hormone refractory prostate cancer."Cancer Sci.. in press. (2004)
[Publications] W.Kumamaru, S.Nakamura, T.Kadena, A.Yamada, E.Kawamura, M.Sasaki, Y.Ohyama, T.Toyoshima, J.Hayashida, K.Itoh, K.Shirasuna: "T cell receptor Vβ gene usage by T cells reactive with the tumor rejection antigen SART-1 in oral squamous cell carcinoma."Int.J.Cancer. in press. (2004)
[Publications] N.Tsuda, K.Mochizuki, M.Harada, A.Sukehiro, K.Kawano, A.Yamada, K.Ushijima, T.Sugiyama, T.Nishida, H.Yamana, K.Itoh, T.Kamura: "Vaccination with pre-designated or evidence-based peptides for patients with recurrent gynecologic cancers."J.Immunother.. 27. 60-67 (2004)
[Publications] Y.Sato, H.Shomura, Y.Maeda, T.Mine, Y.Une, Y.Akasaka, M.Kondo, S.Takahashi, T.Shinohara, K.Katagiri, M.Sato, S.Okada, K.Matsui, A.Yamada, H.Yamana, K.Itoh, S.Todo: "Immunological evaluation of peptide vaccination for patients with gastric cancer based on pre-existing cellular response to peptide."Cancer Sci.. 94. 802-808 (2003)
[Publications] S.Ohkouchi, N.Kawamoto, F.Sakanashi, S.Shichijo, Y.Saijo, T.Nukiwa, K.Itoh, A.Yamada: "Identification of cytotoxic T lymphocyte-directed epitope encoded by an intron of putative tumor suppresser gene Testin of the common fragile site 7G region at 7q31.2: Peptide vaccine candidate for HLA-B52^+ and -62^+ cancer patients."Eur.J.Immunol.. 33. 2964-2973 (2003)
[Publications] N.Ikewaki, A.Yamada, H.Inoko: "Depolymerization of actin filament by cytochalasin E induces interleukin-8 production and up-regulates CD54 in the Hela epithelial cell line."Microbiol.Immunol.. 47. 775-783 (2003)
[Publications] T.Mine, R.Gouhara, N.Hida, N.Imai, K.Azuma, T.Rikimaru, K.Katagiri, M.Nishikori, A.Sukehiro, M.Nakagawa, A.Yamada, H.Aizawa, K.Shirouzu, K.Itoh, H.Yamana: "Immunological evaluation of CTL precursor-oriented vaccines for advanced lung cancer patients."Cancer Sci.. 94. 548-556 (2003)
[Publications] S.Tanaka, M.Harada, T.Mine, M.Noguchi, R.Gohara, K.Azuma, M.Tamura, A.Yamada, A.Morinaga, M.Nishikori, K.Katagiri, K.Itoh, H.Yamana, T.Hashimoto: "Peptide vaccination for patients with melanoma and other types of cancers based on pre-existing peptide-specific cytotoxic T lymphocyte precursors in the periphery."J.Immunother.. 26. 357-366 (2003)
[Publications] M.Noguchi, K.Kobayashi, N.Suetsugu, K.Tomiyasu, S.Suekane, A.Yamada, K.Itoh, S.Noda: "Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination."Prostate. 57. 80-92 (2003)
[Publications] N.Kawamoto, S.Ohkouchi, T.Maeda, S.Tanaka, T.Hashimoto, S.Saijo, Y.Saijo, S.Shichijo, K.Itoh, A.Yamada: "IgG reactive to CTL-directed epitope peptides is either lacking or unbalanced in atopic dermatitis patients."Tissue Antigens. 61. 352-361 (2003)
[Publications] A.Yamada, K.Kawano, M.Koga, S.Takamori, M.Nakagawa, K.Itoh: "Gene and peptide analyses of newly defined lung cancer rejection antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes."Cancer Res.. 63. 2829-2835 (2003)
[Publications] M.Koga, S.Shichijo, A.Yamada, J.Ashihara, H.Sawamizu, J.Kusukawa, K.Itoh: "Identification of ribosomal proteins S2 and L10a as tumor-rejection antigens recognized by HLA-A26-restricted CTL."Tissue Antigens. 61. 136-145 (2003)

2003 Fiscal Year Annual Research Report

新規肺癌抗原の同定とそれらを分子標的としたペプチドワクチンの開発

Principal Investigator

山田 亮 久留米大学, 先端癌治療研究センター, 教授 (50158177)

Research Products

[Publications] M.Koga, N.Komatsu, S.Shichijo, K.Itoh, A.Yamada: "Analysis of cellular localization of SART3 tumor antigen by newly established monoclonal antibody : Heterotopic expression of SART3 tumor antigen on the surface of B-lineage leukemic cells."Oncol.Reports. in press. (2004)

[Publications] Y.Sato, Y.Maeda, T.Sasatomi, M.Takahashi, Y.Une, M.Kondo, T.Shinohara, N.Hida, K.Katagiri, K.Sato, A.Yamada, H.Yamana, K.Itoh, S.Todo: "A phase I trial of CTL-purecursor-oriented peptide vaccine for colorectal carcinoma patients."Br.J.Cancer. in press. (2004)

[Publications] M.Noguchi, K.Itoh, S.Suekane, A.Yao, N.Suetsugu, K.Katagiri, A.Yamada, H.Yamana, S.Noda: "Phase I trial of patient-oriented vaccination in HLA-A2 positive patients with metastatic hormone refractory prostate cancer."Cancer Sci.. in press. (2004)

[Publications] W.Kumamaru, S.Nakamura, T.Kadena, A.Yamada, E.Kawamura, M.Sasaki, Y.Ohyama, T.Toyoshima, J.Hayashida, K.Itoh, K.Shirasuna: "T cell receptor Vβ gene usage by T cells reactive with the tumor rejection antigen SART-1 in oral squamous cell carcinoma."Int.J.Cancer. in press. (2004)

[Publications] N.Tsuda, K.Mochizuki, M.Harada, A.Sukehiro, K.Kawano, A.Yamada, K.Ushijima, T.Sugiyama, T.Nishida, H.Yamana, K.Itoh, T.Kamura: "Vaccination with pre-designated or evidence-based peptides for patients with recurrent gynecologic cancers."J.Immunother.. 27. 60-67 (2004)

[Publications] N.Ikewaki, A.Yamada, H.Inoko: "Depolymerization of actin filament by cytochalasin E induces interleukin-8 production and up-regulates CD54 in the Hela epithelial cell line."Microbiol.Immunol.. 47. 775-783 (2003)

[Publications] T.Mine, R.Gouhara, N.Hida, N.Imai, K.Azuma, T.Rikimaru, K.Katagiri, M.Nishikori, A.Sukehiro, M.Nakagawa, A.Yamada, H.Aizawa, K.Shirouzu, K.Itoh, H.Yamana: "Immunological evaluation of CTL precursor-oriented vaccines for advanced lung cancer patients."Cancer Sci.. 94. 548-556 (2003)

[Publications] M.Noguchi, K.Kobayashi, N.Suetsugu, K.Tomiyasu, S.Suekane, A.Yamada, K.Itoh, S.Noda: "Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination."Prostate. 57. 80-92 (2003)

[Publications] N.Kawamoto, S.Ohkouchi, T.Maeda, S.Tanaka, T.Hashimoto, S.Saijo, Y.Saijo, S.Shichijo, K.Itoh, A.Yamada: "IgG reactive to CTL-directed epitope peptides is either lacking or unbalanced in atopic dermatitis patients."Tissue Antigens. 61. 352-361 (2003)

[Publications] A.Yamada, K.Kawano, M.Koga, S.Takamori, M.Nakagawa, K.Itoh: "Gene and peptide analyses of newly defined lung cancer rejection antigens recognized by HLA-A2402-restricted tumor-specific cytotoxic T lymphocytes."Cancer Res.. 63. 2829-2835 (2003)

[Publications] M.Koga, S.Shichijo, A.Yamada, J.Ashihara, H.Sawamizu, J.Kusukawa, K.Itoh: "Identification of ribosomal proteins S2 and L10a as tumor-rejection antigens recognized by HLA-A26-restricted CTL."Tissue Antigens. 61. 136-145 (2003)

山田亮久留米大学, 先端癌治療研究センター, 教授 (50158177)