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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
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥10,800,000 (Direct Cost: ¥10,800,000)
Keywordsin vitro immunization / human antibody / adjuvant / phaze display method / allergen / TNF-α / antibody for peptides / large-scale production / ファージディスプレー法 / コメアレルゲン / アレルギー / IgE
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.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (34 results)

All 2005 2004 2003 2002 Other

All Journal Article (19 results) Book (5 results) Patent(Industrial Property Rights) (2 results) Publications (8 results)

  • [Journal Article] A role of monocyte in controlling peripheral immune response.2005

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

      Animal Cell Technology : Basic & Applied Aspects 14(印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Efficient cloning method for variable region genes of antigen specific human monoclonal antibody.2005

    • Author(s)
      S.Matsumoto et al.
    • Journal Title

      Animal Cell Technology : Basic & Applied Aspects 14(印刷中)

    • Related Report
      2004 Annual Research Report
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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

    • NAID

      130000030915

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] IL-10 augments antibody production in in vitro immunized lymphocytes by inducing a Th2-type response and B cell maturation2004

    • Author(s)
      Q.Xu et al.
    • Journal Title

      Bioscience, Biotechnology and Biochemistry 68・11

      Pages: 2279-2284

    • Related Report
      2004 Annual Research Report
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Different individual immune responses elicited by in vitro immunization.2003

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

      Cytotechnology 40・1-3

      Pages: 161-165

    • Related Report
      2004 Annual Research Report
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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

    • NAID

      110002693509

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Construction of an in vitro allergy reaction evaluation systems using human leukemia cell lines.2002

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

      Cytotechnology 40・1-3

      Pages: 75-83

    • Related Report
      2004 Annual Research Report
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
    • Related Report
      2004 Final Research Report Summary
  • [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
      2003-314731
    • Filing Date
      2003-09-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [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 他3名
    • Industrial Property Rights Holder
      (独)科学技術振興機構
    • Filing Date
      2003-09-05
    • Related Report
      2004 Annual Research Report
  • [Publications] M.Yamashita et al.: "Different individual immune responses by in vitro immunization"Cytotechnology. 4・1-3. 161-171 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.-Y.Shim et al.: "Construction of an in vitro allergy reaction evaluation system using human leukemia cell lines"Cytotechnology. 4・1-3. 75-83 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.-Y.Shim et al.: "Production of genetically engineered antigen specific human monoclonal IgE antibody"Animal Cell Technology : Basic & Applied Aspects. 12. 225-229 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] M.Yamashita et al.: "CD8^+ T cells negatively regulate the antibody production from the human PBMC being immunized in vitro with antigen"Animal Cell Technology : Basic & Applied Aspects. 12. 231-234 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Makiko Yamashita, et al.: "Different individual immune response elicited by in vitro immunization"Cytotechnology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sum Yup Shim, et al.: "Construction of in vitro allergy reaction evaluation system using human leukemia cell lines"Cytotechnology. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sum Yup Shim, et al.: "Production of genetically engineered antigen specific human monoclonal lgE antibody"Animal Cell Technology for Creation of New Era. 225-229 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Makiko Yamashita, et al.: "CD8+T cells negatively regulate the antibody production from the human PBMC being immunized vitro with antigen"Animal Cell Technology for Creation of New Era. 231-234 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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