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Development of a tumor vaccine using a membrane attached form of interleukin-15

Research Project

Project/Area Number 09670782
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

MINEGISHI Masayoshi (1998)  Institute of Development, Aging and Cancer, Department of Pediatric Oncology Tohoku University Associate Professor, 加齢医学研究所・発達病態研究分野, 助教授 (20211592)

今野 多助 (1997)  東北大学, 加齢医学研究所, 教授 (00004846)

Co-Investigator(Kenkyū-buntansha) KONNO Tasuke  Institute of Development, Aging and Cancer, Department of Pediatric Oncology Toh, 加齢医学研究所・発達病態研究分野, 前教授 (00004846)
KUMAKI Satoru  Institute of Development, Aging and Cancer, Department of Pediatric Oncology Toh, 加齢医学研究所・発達病態研究分野, 助手
藤江 弘美  東北大学, 加齢医学研究所, 助手 (60282000)
峯岸 正好  東北大学, 加齢医学研究所, 助手 (20211592)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsinterleukin-15 / acute GVHD / gammac chain / NK cell / retrovirus vector / リーダー配列 / X連鎖重症複合免疫不全症
Research Abstract

To evaluate factors affect IL-15 production, we examined serum levels of IL-15 in children who had received allogeneic BMT as a model of immune reconstitution. We observed prolonged secretion of IL-15 only in patients with grade III or IV acute OVHD.Since 11-15 is able to activate antigen-stimulated T cells and NK cells, IL-15may play an important role in the development of severe forms of acute GVHD.We also examined functional role of 11-15 using a mutant gammac chain (A156V) isolated from an atypical X-SCID patient who lacked T cells but has normal NK activity. We demonstrate that the mutant gammac chain transduces an IL-15-induced signal. Therefore, the mutant gammac chain might be partially functional for NK-cell development and as a result the patient has NK cells. IL-15 protein has been harder to detect, although IL-15 mRNA is found almost everywhere. One of the reasons for this inefficient translation is the unusually long IL-15 leader. Thus, we replaced the leader sequence with that of IL-2and inserted into a retrovirus vector, pLXIN.With this construct, IL-15 was produced much more efficiently than with the wild type IL-15 cDNA.In addition, a cell surface-bound form of IL-15 was constructed with this highly efficient IL-15 plus transmembrane region of the chain. The chimeric protein failed to express on the cell surface. We speculated that the IL-2 leader might interrupt the cell surface expression and now replacing the leader sequence with that of the gammac chain. Meanwhile, we are establishing an autocrine cell line by infection of the retrovirus encoding the highly efficient IL-15 cDNA to cells obtained from a patient with stem cell leukemia, which express a high level of functional IL-15 receptor. We are planning to develop a tumor vaccine using the retrovirus vectors and the autorine cell line described above.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kumaki S.et al.: "Prolonged secretion of IL-15 in patients with severe forms of acute GVHD after allogeneic bone marrow transplantation in children." Int J Hematol. 67. 307-312 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S.et al.: "A novel mutant γc chain from a patient with typical phenotype of X-SCID has partial signaling function for mediating IL-2- and IL-4-receptor action." Clin Exp Immunol. 115. 356-361 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S.et al.: "Functional role of IL-4 and IL-7 in the development of X-linked severe combined immunodeficiency." Blood. 93. 607-612 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawamura M.et al.: "Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia." Leukemia Res.23. 115-126 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hossain A.et al.: "The Ah receptor is not involved in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines." J Biol Chem. 273. 19853-19858 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S., Minegishi M., Fujie H., Sasahara Y., Ohashi Y., Tsuchiya S.and Konno T.: "Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus-host disease after allogeneic bone marrow transplantation in children." Int J Hematol. 67. 307-312 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hossain A., Tsuchiya S., Minegishi M., Osada M., Ikawa S., Tezuka FA., Kaji M., Konno T., Watanabe M.and Kikuchi H.: "The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines." J Biol Chem. 273. 19853-19858 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S., Ochs H.D., Kuropatwinski K.K., Konno T.: "Timour M.S., Cosman D.and Baumann H., A novel mutant gc chain from a patient with typical phenotype of X-linked severe combined immunodeficiency has partial signaling function for mediating IL-2-and IL-4-receptor action." Clin Exp Immunol. 115. 356-361 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S., Ishii N., Minegishi M., Tsuchiya S.: "Cosman D., Sugamura K.and Konno T.Functional role of IL-4 and IL-7 in the development of X-linked severe combined immunodeficiency" Blood. 93. 607-612 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawamura M., Ohnishi H., Guo SX., Sheng XM., Minegishi M., Hanada R., Horibe K., Hongo T., Kaneko Y., Bessho F., Yanagisawa M., Sekiya T., Hayashi Y.: "Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia." Leukemia Res.23. 115-126 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumaki S., Minegishi M., Konno T.et al.: "Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus-host disease after allogeneic bone marrow transplantation in children." Int J Hematol. 67. 307-312 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kumaki S., Konno T.et al: "A novel mutant γc chain from a patient with typical phenotype of X-SCID has partial signaling function for mediating IL-2-and IL-4-receptor action." Clin Exp Immunol. 115. 356-361 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kumaki S., Minegishi M., Konno T.et al.: "Functional role of IL-4 and IL-7 in the development of X-linked severe combined immunodeficiency." Blood. 93. 607-612 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawamura M., Minegishi M.et al.: "Alterations of the p53, p21, p16, p15, and RAS genes in childhood T-cell acute lymphoblastic leukemia," Leukemia Res.23. 115-126 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hossain A., Minegishi M.et al.: "The Ah receptor is not involved in 2, 3, 7, 8, -tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines." J Biol Chem. 273. 19853-19858 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Satoru Kumaki, Masayoahi Minegishi, Tasuke Konno et.al.: "Prolonged secretionof IL-15 in patients with severe forms of acute graft-versus-host disease after allogeneic bone marrow transplantation in children" International Journal of Hematology. (in press).

    • Related Report
      1997 Annual Research Report

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

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