2002 Fiscal Year Annual Research Report

キラーT細胞により認識される肺癌拒絶抗原遺伝子の同定と癌ワクチンの開発

Research Project

Project/Area Number	12670583
Research Institution	KURUME UNIVERSITY
Principal Investigator	山田亮久留米大学, 医学部, 助教授 (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	肺癌細胞株11-18より作製したcDNAライブラリーよりHLA-A2402拘束性CTL株GK-CTLを用いてgene expression cloning法によりHLA-A24拘束性肺腺癌拒絶抗原遺伝子のクローニングを行い、7個の遺伝子クローンを得た。これらのクローンについてHLA-A2402拘束性が確認されたので、全塩基配列を決定した。その結果、3個は既知の遺伝子であり、4個は新規遺伝子であった。さらに、Northern blottingによりメッセージサイズを決定した。これら7個の遺伝子のうちの一つ、抗癌剤に対する多剤耐性(MDR)に関連したタンパクであるmultidrug resi stance associated protein 3 (MRP3)をコードする遺伝子については前年度に癌抗原ペプチドの同定を行った。そこで、本年度は他の遺伝子について詳細な検討を加えた。HLA-A24結合性ペプチドのモチーフはすでに決定されているので、HLA-A24結合モチーフを有する9ないし10アミノ酸からなるペプチドを選別し、これらの合成ペプチドをHLA-A2402安定形質転換細胞株C1R-A2402にパルスし、GK-CTLとの反応性をIFN-_γ産生で検討した。その結果6個の遺伝子由来の計13個のHLA-A24拘束性癌拒絶抗原ペプチドを同定した。さらに、これらのペプチドによるHLA-A24陽性の健常人もしくは肺癌患者末梢血リンパ球からのペプチド特異的CTLの誘導を試みた。その結果、肺癌患者の末梢血からHLA-A24拘束性ペプチド特異的CTLが誘導され、細胞傷害活性も確認された。これら遺伝子の各種癌細胞におけるmRNA発現を調べたところ、肺癌細胞株全例(n=10)に発現が認められ、癌組織においても発現が確認された。

Research Products

(29 results)

All Other

All Publications (29 results)

[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. (in press). (2003)
[Publications] M.Noguchi, K.Kobayashi, N.Suetsugu, K.Tomiyasu, S.Suekane, A.Yamada, K.Itoh, S.Noda: "Induction fo cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination"Prostate. (in press). (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・5. 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-restriced tumor-specific cytotoxic T lymphocytes"Cancer Res. 63・11. 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・2. 136-145 (2003)
[Publications] A.Yamada, H.Yamana, K.Itoh: "Development of peptide-based vaccines for epithelial cancer"In"Research Progress in Cancer 2", R. M. Mohan (Ed), Global Research Network, India. 241-247 (2002)
[Publications] N.Tsuda, Y.Nonaka, S.Shichijo, A.Yamada, M.Ito, Y.Maeda, M.Harada, T.Kamura, K.Itoh: "UDP-Gal : βGlcNAc 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・9. 1006-1012 (2002)
[Publications] R.Gohara, N.Imai, T.Rikimaru, A.Yamada, M.Ichiki, M.Kawamoto, K.Matsunaga, J.Ashihara, S.Yano, S.Ohkouchi, H.Yamana, K.Oizumi, K.Itoh: "Cellular and humoral immune responses to tumor cells and peptides in lung cancer patients vaccinated with cyclophilinB peptide"J. Immunother. 25・5. 439-444 (2002)
[Publications] K.Noda, K.Tanaka, A.Yamada, J.Ogata, H.Tanaka, Y.Shoyama: "Simple assay for antitumor immuno-active glycoprotein derived from Chlorella vulgaris strain CK22 using ELISA"Phytother. Res. 16・6. 581-585 (2002)
[Publications] S.Ohkouchi, A.Yamada, N.Imai, T.Mine, K.Harada, S.Shichijo, Y.Maeda, Y.Saijo, T.Nukiwa, K.Itoh: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of healthy individuals"Tissue Antigens. 59・4. 259-272 (2002)
[Publications] Y.Miyagi, N.Imai, T.Sasatomi, A.Yamada, T.Mine, K.Katagiri, M.Nakagawa, A.Muto, S.Okouchi, H.Isamoto, K.Shirouzu, H.Yamana, K.Itoh: "Induction of cellular immune responses to tumor cells and peptides in colorectal cancer patients by vaccination of SART3 peptides"Clin. Cancer Res. 7・12. 3950-3962 (2001)
[Publications] M.Imai, N.Harashima, M.Ito, Y.Miyagi, M.Harada, A.Yamada, K.Itoh: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94・2. 237-242 (2001)
[Publications] A.Yamada, K.kawano, M.Koga, T.Matsumoto, K.Itoh: "Multidrug resistance-associated protein 3 (MRP3) is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res. 61・17. 6459-6466 (2001)
[Publications] N.Imai, N.Harashima, M.Ito, Y.Miyagi, M.Harada, A.Yamada, K.Itoh: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94・2. 237-242 (2001)
[Publications] A.Yamada, K.Kawano, M.Koga, T.Matsumoto, K.Itoh: "Multidrug resistance-associated protein 3 (MRP3) is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res. 61・17. 6459-6466 (2001)
[Publications] K.Harada, A.Yamada, D.Yang, K.Itoh, S.Shichijo: "Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1 : a possible regulation of splicing by the complex formation"Int. J. Cancer. 93・5. 623-628 (2001)
[Publications] M.Tsuru, K.Nagata, T.Ueno, A.Jimi, K.Irie, A.Yamada, T.Nishida, M.Sata: "Electron microscopic observation of established chondrocytes derived from human intervertebral disc hernia (KTN-1) and role of macrophages in spontaneous regression of degenerated tissues"Spine J. 1. 422-431 (2001)
[Publications] N.Tsuda, K.Murayama, H.Ishida, K.Matsunaga, S.Komiya, K.Itoh, A.Yamada: "Expression of a newly defined tumor-rejection antigen SART3 in musculoskeletal tumors and induction of HLA class I-restricted cytotoxic T lymphocytes by SART3-derived peptides"J. Orthopaed. Res. 19・3. 346-351 (2001)
[Publications] N.Harashima, K.Tanaka, T.Sasadomi, K.Shimizu, Y.Miyagi, A.Yamada, M.Tamura, H.Yamana, K.Itoh, S.Shichijo: "Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of metastatic cancer patients"Eur. J. Immunol. 31・2. 323-332 (2001)
[Publications] T.Hasegawa, K.Noda, S.Kumamoto, Y.Ando, A.Yamada, Y.Yoshikai: "Chlorella vulgaris supernatant (CVS) reduces psychological stress-induced apoptosis in thymocytes of mice"Int. J. Immunopharmacol. 22・11. 877-885 (2000)
[Publications] N.Ikewaki, H.Tamauchi, A.Yamada, M.Aoki, R.Yamamoto, A.Sawada, H.Inoko: "A microfilament formation inhibitor, cytochalasin, strongly enhances the low affinity Fc-ε receptor II (CD23) expression on the human monocyte-like cell line, U937"J. Clin. Immunol. 20・6. 424-433 (2000)
[Publications] K.Shimizu, S.Fujii, K.Fujimoto, K.Kawa, A.Yamada, F.Kawano: "Tacrolimus (FK506) treatment of CD34^+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4^+ T cells toward Th2 responses"J. Leukocyte Biol. 68・5. 633-640 (2000)
[Publications] K.Kawano, S.Gomi, K.Tanaka, T.Kamura, K.Itoh, A.Yamada: "Identification of a new endoplasmic reticulum-resident protein recognized by HLA-A24-restricted tumor infiltrating lymphocytes of lung cancer"Cancer Res. 60・13. 3550-3358 (2000)
[Publications] T.Mine, K.Harada, T.Matsumoto, H.Yamana, K.Shirouzu, K.Itoh, A.Yamada: "CDw108 expression during T-cell development"Tissue Antigens. 55・5. 429-436 (2000)
[Publications] N.Ikewaki, H.Tamauchi, A.Yamada, N.Mori, Y.Fukumoto, R.Shibata, H.Yamao, H.Inoue, H.Inoko: "A unique monoclonal antibody m NI-11 rapidly enhances spread formation in human umbilical vein endothelial cells (HUVECs)"J. Clin. Immunol. 20・4. 317-324 (2000)
[Publications] M.Nakao, S.Shichijo, T.Imaizumi, Y.Inoue, K.Matsunaga, A.Yamada, M.Kikuchi, N.Tsuda, K.Ohta, S.Takamori, H.Yamana, H.Fujita, K.Itoh: "Identification of a gene coding for a new squamous cell carcinoma antigen recognized by the cytotoxic T lymphocytes"J. Immunol. 164・5. 2565-2575 (2000)
[Publications] K.Harada, A.Yamada, T.Mine, N.Kawagoe, H.Takasu, K.Itoh: "Mouse homologue of human SART3 gene encoding tumor rejection antigen"Jap. J. Cancer Res. 91・2. 239-247 (2000)
[Publications] H.Kawagoe, A.Yamada, H.Matsumoto, M.Itoh, K.Ushijima, T.Nishida, K.Itoh: "Serum MAGE-4 protein in ovarian cancer patients"Gynecologic Oncol. 76・3. 336-339 (2001)
[Publications] N.Seki, A.Yamada, Y.Suefuji, T.Mine, S.tanaka, S.Gomi, N.Kawagoe, K.Koufuji, K.Itoh: "Establishment and epitope analysis of allo-specific cytotoxic T lymphocytes at a tumor site recognizing a spouse's HLA-A0206 molecule"Am. J. Reprod. Immunol. 43・3. 167-173 (2000)

2002 Fiscal Year Annual Research Report

キラーT細胞により認識される肺癌拒絶抗原遺伝子の同定と癌ワクチンの開発

Principal Investigator

山田 亮 久留米大学, 医学部, 助教授 (50158177)

Research Products

[Publications] M.Noguchi, K.Kobayashi, N.Suetsugu, K.Tomiyasu, S.Suekane, A.Yamada, K.Itoh, S.Noda: "Induction fo cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination"Prostate. (in press). (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・5. 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-restriced tumor-specific cytotoxic T lymphocytes"Cancer Res. 63・11. 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・2. 136-145 (2003)

[Publications] A.Yamada, H.Yamana, K.Itoh: "Development of peptide-based vaccines for epithelial cancer"In"Research Progress in Cancer 2", R. M. Mohan (Ed), Global Research Network, India. 241-247 (2002)

[Publications] K.Noda, K.Tanaka, A.Yamada, J.Ogata, H.Tanaka, Y.Shoyama: "Simple assay for antitumor immuno-active glycoprotein derived from Chlorella vulgaris strain CK22 using ELISA"Phytother. Res. 16・6. 581-585 (2002)

[Publications] S.Ohkouchi, A.Yamada, N.Imai, T.Mine, K.Harada, S.Shichijo, Y.Maeda, Y.Saijo, T.Nukiwa, K.Itoh: "Non-mutated tumor-rejection antigen peptides elicit type-I allergy in the majority of healthy individuals"Tissue Antigens. 59・4. 259-272 (2002)

[Publications] M.Imai, N.Harashima, M.Ito, Y.Miyagi, M.Harada, A.Yamada, K.Itoh: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94・2. 237-242 (2001)

[Publications] A.Yamada, K.kawano, M.Koga, T.Matsumoto, K.Itoh: "Multidrug resistance-associated protein 3 (MRP3) is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res. 61・17. 6459-6466 (2001)

[Publications] N.Imai, N.Harashima, M.Ito, Y.Miyagi, M.Harada, A.Yamada, K.Itoh: "Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases"Int. J. Cancer. 94・2. 237-242 (2001)

[Publications] A.Yamada, K.Kawano, M.Koga, T.Matsumoto, K.Itoh: "Multidrug resistance-associated protein 3 (MRP3) is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes"Cancer Res. 61・17. 6459-6466 (2001)

[Publications] K.Harada, A.Yamada, D.Yang, K.Itoh, S.Shichijo: "Binding of a SART3 tumor-rejection antigen to a pre-mRNA splicing factor RNPS1 : a possible regulation of splicing by the complex formation"Int. J. Cancer. 93・5. 623-628 (2001)

[Publications] N.Harashima, K.Tanaka, T.Sasadomi, K.Shimizu, Y.Miyagi, A.Yamada, M.Tamura, H.Yamana, K.Itoh, S.Shichijo: "Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of metastatic cancer patients"Eur. J. Immunol. 31・2. 323-332 (2001)

[Publications] T.Hasegawa, K.Noda, S.Kumamoto, Y.Ando, A.Yamada, Y.Yoshikai: "Chlorella vulgaris supernatant (CVS) reduces psychological stress-induced apoptosis in thymocytes of mice"Int. J. Immunopharmacol. 22・11. 877-885 (2000)

[Publications] N.Ikewaki, H.Tamauchi, A.Yamada, M.Aoki, R.Yamamoto, A.Sawada, H.Inoko: "A microfilament formation inhibitor, cytochalasin, strongly enhances the low affinity Fc-ε receptor II (CD23) expression on the human monocyte-like cell line, U937"J. Clin. Immunol. 20・6. 424-433 (2000)

[Publications] K.Shimizu, S.Fujii, K.Fujimoto, K.Kawa, A.Yamada, F.Kawano: "Tacrolimus (FK506) treatment of CD34^+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4^+ T cells toward Th2 responses"J. Leukocyte Biol. 68・5. 633-640 (2000)

[Publications] K.Kawano, S.Gomi, K.Tanaka, T.Kamura, K.Itoh, A.Yamada: "Identification of a new endoplasmic reticulum-resident protein recognized by HLA-A24-restricted tumor infiltrating lymphocytes of lung cancer"Cancer Res. 60・13. 3550-3358 (2000)

[Publications] T.Mine, K.Harada, T.Matsumoto, H.Yamana, K.Shirouzu, K.Itoh, A.Yamada: "CDw108 expression during T-cell development"Tissue Antigens. 55・5. 429-436 (2000)

[Publications] N.Ikewaki, H.Tamauchi, A.Yamada, N.Mori, Y.Fukumoto, R.Shibata, H.Yamao, H.Inoue, H.Inoko: "A unique monoclonal antibody m NI-11 rapidly enhances spread formation in human umbilical vein endothelial cells (HUVECs)"J. Clin. Immunol. 20・4. 317-324 (2000)

[Publications] K.Harada, A.Yamada, T.Mine, N.Kawagoe, H.Takasu, K.Itoh: "Mouse homologue of human SART3 gene encoding tumor rejection antigen"Jap. J. Cancer Res. 91・2. 239-247 (2000)

[Publications] H.Kawagoe, A.Yamada, H.Matsumoto, M.Itoh, K.Ushijima, T.Nishida, K.Itoh: "Serum MAGE-4 protein in ovarian cancer patients"Gynecologic Oncol. 76・3. 336-339 (2001)

[Publications] N.Seki, A.Yamada, Y.Suefuji, T.Mine, S.tanaka, S.Gomi, N.Kawagoe, K.Koufuji, K.Itoh: "Establishment and epitope analysis of allo-specific cytotoxic T lymphocytes at a tumor site recognizing a spouse's HLA-A0206 molecule"Am. J. Reprod. Immunol. 43・3. 167-173 (2000)

山田亮久留米大学, 医学部, 助教授 (50158177)