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Identification of genes encoding tumor-rejection antigens of cancers from digestive tract and development of cancer vaccine

Research Project

Project/Area Number 09470271
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKurume University School of Medicine

Principal Investigator

ITOH Kyogo  Kurume Univ.Sch.Med., Dep.Immunol., Professor, 医学部, 教授 (50125499)

Co-Investigator(Kenkyū-buntansha) 五味 慎也  久留米大学, 医学部, 助手 (30289368)
IMAI Yasuhisa  Kurume Univ.Sch.Med., Research Associate, 医学部, 助手 (90268847)
NAKAO Masanobu  Kurume Univ.Sch.Med., Dep.Immunol., Lecturer, 医学部, 講師 (40258447)
YAMADA Hideaki  Kurume Univ.Sch.Med., Dep.Surg., Associate Professor, 医学部, 助教授 (30140669)
ISOMOTO Hiroharu  Kurume Univ.Sch.Med., Dep.Surg., Professor, 医学部, 教授 (80080745)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1998: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1997: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordscancer of digestive tract / tumor-rejection antigen / gene cloning / cancer vaccine / HLA-class I / SART1 / Peptide antigen / HLA-クラスI
Research Abstract

1) Detection of specific immunity at the tumor sites of digestive tract. One of the fundamental questions in human tumor immunology is whether HLA-class I-restricted and tumor-specific CTLs exist in tumor sites of cancers originated from digestive tract. or not. We have been addressing this question by testing CTL activity of T cells infiltrating into the various cancers of digestive tract after in vitro incubation with interleukin-2. The results showed the presence of HLA-class I-restricted and tumorspecific CTLs at the tumor sites in all the cancer tested, including esophageal cancers, gastric cancers, and colon cancers. For detailed characterization of these CTLs, please see the manuscripts in the peer-reviewed journals that are attached as appendices 1 (CTLs at the sites of esophageal cancers), 2 (CTLs at gastric cancers), and 3 (CtLs at colon cancers)
2) Identification of genes encoding tumor-rejection antigens from cancer of digestive tract. The second question in the human tumor … More immunology is whats' molecules are recognized by these CTLs. Four new genes (SART1, SART2, SART3, and SART4) encoding tumor-rejection antigens have been cloned from cDNA library of human esophageal cancer cells. The peptides encoded by these genes are recognized by either HLA-A24 or-A26-restricted CTLs. HLA-A24 or-A26 allele is found in 60 or 22 % of Japanese. Some of these peptides have the strong activity to induce HLA-class I-restricted CTLs capable of lysing tumor cells. Further, antigens encoded by these genes are highly expressed in cancers of digestive tracts, including head and neck cancers, esophageal cancers, gastric cancers, and colorectal cancers. Therefore, these peptides could be available for relatively large number of cancer patients of digestive tract. For the detailed characterization of SART1 gene, please see the manuscripts in the peer-reviewed journals that re attached as appendices 4 (identification of SART1 gene), 5 (induction of CTLs by the SART1 peptides), 6 (SART1 expression in breast cancer), and 7 (SART1 expression in head and neck cancers). The manuscripts on the SART2 and SART3 genes are under submission for the journals, and that on SART4 genes is in preparation. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (43 results)

All Other

All Publications (43 results)

  • [Publications] Hoshino, T., Itoh, K., et al: "HLA-class 1-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer." Int.J.Cancer. 70. 631-638 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toh, U., Itoh, K., et al.: "HLA-class-1-restricted and tumor-specific cytotoxic 1 lymphocytes from matastatic lymphocytes from metastatic lympho nodes of esophageal cancers" Cell. Immunol.177. 137-143 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shichijo, S., Itoh, K., et al: "A Gene encoding antlgenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes." J.Exp.Med.187. 277-288 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Etoh, O., Itoh, K., et al: "Active Immunotherapy with ultravlolet-B Irradiated autologous whole melanoma cells plus Detox^<TM> in patlents with metastatic melanoma." Clinical Cancer Research. 4. 619-627 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawamoto, M., Itoh, K.et al: "Expression of the SART-1 tumor-rejection antlgen In breast cancer." Int.J.Cancer. 80. 64-67 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kikuchi, M., Itoh, K.et al: "Identification of a SART-1-derived peptolde capable of Inducing the HLA-A24-restricted and tumor-speclfic cytotoxic T lymphocytes." Int.J.Cancer. in press (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itoh, K., et al: "In : International Reviews ; of Immunology" Springer-Verlag, New York, (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shichijo, S., Itoh, K., et al: "Japan GannMonograph on CancerResearch No.48" Sclentific Socletles Press, Tokyo in press, (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Sudo, T., Kuramoto, T., Komiya, S., Inoue, A., Itoh, K.: "Expression of MAGE genes in osteosarcoma" J.Orthopaedic Research. 15. 128-132 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyajima, J., Imai, Y., Nakao, M., Noda, N., Itoh, K.: "Higher susceptibility of erythropoietin-producing renal cell carcinomas to lysis by lymphokine-activated killer cells." J.Immunotherapy.19. 399-404 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwamoto, O., Nagao, Y., Shichijo, S., Eura, M., Kameyama, T., Itoh, K.: "Detection of MAGE-4 protein in sera of patients with head and neck squamous cell carcinoma." Int.J.Can.70. 287-290 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tamai, M., Yokouchi, M., Komiya, S., Mochizuki, K., Hidaka, S., Narita, S., Inoue, A., Itoh, K.: "Correlation between Vitamin D receptor genotypes and bone mineral density in Japanrase patients with osreoporosis." CALCIFIED TISSUE INTRENATIONAL.60. 229-232 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Seki, N., Hoshino, T., Iwamoto., Hayashi, A., Itoh, K.: "HLA-A locus-restricted and tumor-specific CTL in tumor infiltrating lymphocytes of patients with lung cancer." Cell. Immunol.175. 101-110 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada, A., Hara, A., Inoue, M., Kamizono, S., Higuchi, H., Itoh, K.: "b2-integrin-mediated signal up-regulates counter recepter ICAM-1 expression on human monocyte cell line THP-1 through tyrpsine phosphorylation." Cell. Immunol.178. 9-16 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshino, T., Suzuki, R., Tsuruta, Y., Matsutani, T., Kikuchi, M., Kawamoto, M., Gouhara, R., Shiraishi, T., Mochizuki, M., Itoh, K., Oizumi, K.: "Non-restricted T cell receptor-Va and -Vb gene usage in patients with pulmonary sarcoidosis." Clin. Exp.Immunol.108. 529-538 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Gouhara, R., Nakao, M., Ogata, Y., Isomato, H., Oizumi, K., Itoh, K.: "Histocompatibility leukocyte antigen-2402-restricted cytotoxic T lymphocytes recognizing adenocarcinomas in tumor-infiltrating lymphocytes of patients with colon cancer." JJCR.88. 198-204 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshino, T., Seki, N., Kikuchi, M., kuramoto, T., Kodama, K., Koufuji, K., Iwamoto, O., Takeda, J., and Itoh, K.: "HLA-class I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer." Int.J.Cancer.70. 631-638 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakao, M., Sata, M., Saitsu, H., Yutani, S., Kawamoto, M., Koujiro M., Itoh, K.: "CD4+ heaptic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular carcinoma." Cell.Immunol.177. 176-181 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Toh, U., Yamana, H., Nakao, M., Imai Y., Seki, N., Takasu, H., Kaneshige, T., Fujita, H., Shirouzu, K., Itoh, K.: "HLA-class-I-restricted and tumor-specific cytotoxic T lymphocytes from metastatic lymphocytes from metastatic lympho nodes of esophageal cancers." Cell. Immunol.177. 137-143 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shichijo, S., Hoshino, H., koufuji, K., Hayashi, A., Kawamoto, M., Kikuchi, M., Higuchi, T., Ichiki, M., Oizumi, K., Itoh, K.: "Detection of MAGE-4 protein in sera of lung cancer patients." JJCR.88. 414-419 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai, K., Yamada, A., Eguchi, H., Kato, H., Itoh, K.: "HLA-A2402-restricted and tumor-specific cytotoxic T lymphocytes from tumor infiltrating lymphocytes of a child with Wilm's tumor." Pediatric Reseach.42. 122-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noguchi, M., Miyajima, J., Itoh, K., Noda, S.: "Detection of circulating tumor cells in patients with prostatic cancer useing prostate specific membrane-derived primers in the polymerase chain reaction." Int.J.Urol.4. 374-379 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshino, T., Ohta, A., Yang, D., Kawamoto, M., Kikuchi, M., Inoue, Y., Kamizono, S., Ota, T., Itoh, K., Oizumi, K.: "Elevated serum IL-6, IFN-g and TNF-a levels in patients with adult Stillis disease." J.Rheumatology.(in press.). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagao, Y., Sata, M., Itoh, K., Chiba, I., Komiyama, K., Yanoma, K., Eura, M., Tanikawa, K., Kameyama, T.: "High prevalence of hepatitis C virus antibody and RNA in patients with head and neck squamous cell carcinoma" Hepatology Reseach. 7. 206-212 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuzurahara, S., Sata, M., Iwamoto, S., Shichijo, S., Kojiro, M., Tanikawa, K., Itoh, K.: "Detection of MAGE-4 protein in the sear of Patients with hepatitis-C virus-associated hepatocellular carcinoma and liver cirrhosis." JJCR.88. 915-918 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Suekane, S., Nakao, M., Inoue, M., Noda, S., Itoh, K.: "Histocompatibility leukocyte antigen-2-restricted and tumor-specific cytotoxic T lymphocytes from tumor-infiltrating lymphocytes of patient with testicular embryonal cancer." JJCR.88. 1180-1189 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shichijo, S., Nakao, T., Imai, Y., Takasu, H., Kawamoto, M., Niiya, F., Yang, D., Toh, Y., Yamana, H., Itoh, K.: "A Gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes." J.Exp.Med.187. 277-288 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eton, O., Kharkevitch, D.D., Gianan, M.A., Ross, I., Mansfield, P.F., Lee, J.E., Itoh, K., Pride, M., Bedikian, A.C., Papadopoulos, N.E., Plager, C., Legha, S., Benjamin, R.S., and Balch, C.M.: "Active immunotherapy with ultraviolet-B irradiated autologous whole melanoma cells plus DetoxTM in patients with metastatic melanoma." Clinical Cancer Research.4. 619-627 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi, T., Seki, N., Kamizono, S., Yamada, A., Kimura, A., Kato, H., Itoh, K.: "Polymorphism of the 5*-flanking region of human tumor-necrosis factor (TNF)-a gene in Japanese." Tissue Antigen.51. 605-612 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hoshino,T.,Itoh,K.,et al.: "HLA-class I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer." Int.J.Cancer. 70. 631-638 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Toh,U.,Itoh,K.,et al.: "HLA-class-I-restricted and tumor-specific cytotoxic T lymphocytes from metastatic lymphocytes from metastatic lympho nodes of esophageal cancers" Cell. Immunol.177. 137-143 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shichijo,S.,Itoh,K. et al.: "A Gene encoding antigenic peptides of human squamous cell carcinoma recognized by cytotoxic T lymphocytes." J.Exp.Med.187. 277-288 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Eton,O.,Itoh,K.,et al.: "Active immunotherapy with ultraviolet-B irradiated autologous whole melanoma cells plus Detox^<TM> in patients with metastatic melanoma." Clinical Cancer Research. 4. 619-627 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamoto,M.,Itoh,K. et al.: "Expression of the SART-1 tumor-rejection antigen in breast cancer." Int.J.Cancer. 80. 64-67 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kikuchi,M.,Itoh,K. et al.: "Identification of a SART-1-derived peptoide capable of inducing the HLA-A24- restricted and tumor-specific cytotoxic T lymphocytes." Int.J.Cancer. in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itoh,K.,et al.: "In: International Reviews of Immunology" Springer-Verlag,New York, (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shichijo,S.,Itoh,K.,et al.: "Japan Gann Monograph on Cancer Research No.48" Scientific Societies Press,Tokyo (in press), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Seki,N.,Itoh,K.,et al.: "HLA-A locus-restricted and tumor-specific CTL in tumor infiltrating lymphocytes of patients with lung cancer." Cell.Immunol.175. 101-110 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Toh,U.,Itoh,K.,et al.: "HLA-class-I-restricted and tumor-specific cytotxic T lymphocytes from metastatic lymphocytes from metastaticlympho nodes of esophageal cancers." Cell.Immunol.177. 137-143 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwamoto,O.,Itoh,K.,et al.: "Detection of MAGE-4 protein in sera of patients with head and neck squamous cell carcinoma." Int.J.Cancer. 70. 287-290 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hoshino,T.,Itoh,K.,et al.: "HLA-class I-restricted and tumor-specific CTL in tumor-infiltrating lymphocytes of patients with gastric cancer." Int.J.Cancer. 70. 631-638 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Gouhara,R.,Itoh,K.,et al.: "Histocompatibility Leukocyte Antigen-2402-restricted Cytotoxic T lymphocytes Recognizing Adenocarcinomas in Tumor-infiltrating Lymphocytes of Patients with Colon Cancer." JJCR. 88. 198-204 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shichijo,S.,Itoh,K.,et al.: "A gene encoding antigenic peptides of human squamous Cell carcinoma recognized by cytotoxic T lymphocytes." J.Exp.Med.187. 277-288 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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