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2004 Fiscal Year Final Research Report Summary

Development of tecnologies for production of high affinity human antibodies and its application to specific therapies and risk evaluation.

Research Project

Project/Area Number 14360210
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SHIRAHATA Sanetaka  Kyushu University, Faculty of Agriculture, Professor, 大学院・農学研究院, 教授 (90154377)

Co-Investigator(Kenkyū-buntansha) KATAKURA Yoshinori  Kyushu University, Faculty of Agriculture, Associate Professor, 大学院・農学研究院, 助教授 (50264106)
TERUYA Kiichiro  Kyushu University, Faculty of Agriculture, Research Associate, 大学院・農学研究院, 助手 (10273971)
Project Period (FY) 2002 – 2004
Keywordsin vitro immunization / human antibody / adjuvant / phaze display method / allergen / TNF-α / antibody for peptides / large-scale production
Research Abstract

(1)Clarification of the mechanisms of in vitro immunization : In in vitro immunization, it was indispensable to remove cells suppressing antibody production by treatment of peripheral blood lymphocytes with leucyl methyl ester (LLME). Analysis revealed that target cells of LLME was immature dendritic cells, enabling to develop a new method to efficiently induce in vitro immunization by removing immature dedritic cells, instead of using LLME (patent application). Furthermore, instead of muramyl dipeptide as an adjuvant, CpG oligonudleotides were used to induce B cells secreting antigen-specific antibodies efficiently and reproducibly.
(2)Efficient acquisition of variable region of human antibody genes by usinga hybrid system of in vitro immunization and phage display method : Lymphocytes induced antigen-specific antibody production by in vitro immunization were used for phage display method to obtain variable region of antigen- specific human antibody gene efficiently and reproducibly.
(3)Production of human antibodies for peptides. : In order to enhance the wide use of in vitro immunization method, antibodies far peptides was produced. By using the improved in vitro immunization, induction of B cells secreting antibodies against hydrophilic and hydrophobic regions of TNF-α.
(4)Establishment of CHO cell lines highly producing recombinant human antibodies : By using universal high productive CHO cells, a new system was developed to establish CHO cell lines producing antigen-specific human antibodies in a month.
By developing new technologies for production of human antibodies, the term for developing human antibodies was drastically shortened to several months from several years.

  • Research Products

    (20 results)

All 2004 2003 2002

All Journal Article (14 results) Book (5 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] IL-10 augments antibody production in in vitro immunized lymphocytes by inducing a Th2-type response and B cell maturation.2004

    • Author(s)
      QXu, Q.H.et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 69

      Pages: 2279-2284

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] IL-10 augments antibody production in in vitro immunized lymphocytes by inducing a Th2-type response and B cell maturation.2004

    • Author(s)
      Xu, Q.H., Katakura, Y, Yamashita, M., Fang, S., Tamura, T., Matsumoto, S., Aiba, Y, Teruya, K, Osada, K, Nishikawa, R., Shirahata, S.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 68

      Pages: 2279-2284

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] ヒトモノクローナル抗体作製技術の新展開2003

    • Author(s)
      山下 万貴子 et al.
    • Journal Title

      バイオサイエンスとバイオインダストリー 61

      Pages: 324-327

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A hybrid system using both promoter activation and gene amplification for establishing exogenous protein hyper-producing cell lines.2003

    • Author(s)
      Dong, X.Y.et al.
    • Journal Title

      Cytotechnology 43

      Pages: 11-17

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] New development of technologies for production of human monoclonal antibodies.2003

    • Author(s)
      Yamashita, M., Katakura, Y., Shirahata, S.
    • Journal Title

      Bioscience and Bioindustry 61

      Pages: 324-327

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A hybrid system using both promoter activation and gene amplification for establishing exogenous protein hyper-producing cell lines.2003

    • Author(s)
      Dong, X.Y, Teruya, K, Katakura, Y., Zhang, Y.P., Miura, T., Daimon, Y., Mori, T., Ohashi, H., Shirahata, S.
    • Journal Title

      Cytotechnology 43

      Pages: 11-17

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A regulatable selective system facilitates isolation of heterologous protein hyper-producing mammalian cells without gene amplification.2002

    • Author(s)
      Teruya, K. et al.
    • Journal Title

      Cytotechnology 40

      Pages: 13-22

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Construction of an in vitro allergy reaction evaluation systems using human leukemia cell lines.2002

    • Author(s)
      Shim.S.-Y.et al.
    • Journal Title

      Cytotechnology 40

      Pages: 75-83

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Different individual immune responses elicited by in vitro immunization2002

    • Author(s)
      Yamashita, M. et al.
    • Journal Title

      Cytotechnology 40

      Pages: 161-165

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Increased antibody production by retinoids.2002

    • Author(s)
      Inoue, Y. et al.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 66

      Pages: 215-217

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A regulatable selective system facilitates isolation of heterologous protein hyper-producing mammalian cells without gene amplification.2002

    • Author(s)
      Teruya, K, Zhang, Y.P., Katakura, Y., Shirahata, S.
    • Journal Title

      Cytotechnology 40

      Pages: 13-22

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Construction of an in vitro allergy reaction evaluation system using human leukemia cell lines.2002

    • Author(s)
      Shim, S.Y., Ichikawa, A., Yamashita, M., Katakura, Y., Teruya, K, Mochizuki, Y., Tobinaga, E., Shirahata, S.
    • Journal Title

      Cytotechnology 40

      Pages: 75-83

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Different individual immune responses elicited by in vitro immunization.2002

    • Author(s)
      Yamashita, M., Katakura, Y, Shim, S.Y., Matsumoto, S., Tamura, T., Morihara, K., Aiba, Y, Teruya, K, Tsuchiya, T., Shirahata, S.
    • Journal Title

      Cytotechnology 40

      Pages: 161-165

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increased antibody production by retinoids is related to the fusion partner of human hybridomas.2002

    • Author(s)
      Inoue, Y., Shirahata, S.
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry 66

      Pages: 215-217

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Animal Cell Technology : Basic & Applied Aspects2003

    • Author(s)
      Yamashita, M. et al.
    • Total Pages
      518
    • Publisher
      Kluwer Academic Publishers
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Animal Cell Technology : Basic & Applied Aspects2003

    • Author(s)
      Tamura, T. et al.
    • Total Pages
      518
    • Publisher
      Kluwer Academic Publishers
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Animal Cell Technology Meets Genomics2003

    • Author(s)
      Tamura, T. et al.
    • Total Pages
      813
    • Publisher
      Kluwer Academic Publishers
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Animal Cell Technology Meets Genomics2003

    • Author(s)
      Hu, Q.H.et al.
    • Total Pages
      813
    • Publisher
      Kluwer Academic Publishers
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Animal Cell Technology Meets Genomics2003

    • Author(s)
      Matsumoto, S. et al.
    • Total Pages
      813
    • Publisher
      Kluwer Academic Publishers
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 体外免疫末梢血リンパ球を用いた抗原特異的抗体2003

    • Inventor(s)
      白畑 實隆, 片倉 喜範, 照屋 輝一郎, 山下 万貴子
    • Industrial Property Rights Holder
      独立行政法人化学技術振興機構
    • Industrial Property Number
      特願2003-314731
    • Filing Date
      2003-09-05
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2006-07-11  

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