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Development of human lymphocyte expansion method and its application

Research Project

Project/Area Number 03454298
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionThe University of Tokyo

Principal Investigator

MIKAMO Shinsuke (1992-1993)  The Institute of Medical Science, The University of Tokyo, Assistant, 医科学研究所, 助手 (10107435)

関口 守正 (1991)  東京大学, 医科学研究所, 教授 (60012712)

Co-Investigator(Kenkyū-buntansha) IKEBUCHI Kenji  The Institute of Medical Science, The University of Tokyo, Lecturer, 医科学研究所, 講師 (20175194)
UCHIDA Hisanori  The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (30050420)
SEKIGUCHI Morimasa  The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (60012712)
美甘 晋介  東京大学, 医科学研究所, 助手 (10107435)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsCell transfer therapy / Immobilized CD3 / Immobilized IgG / Proliferation / Apoptosis / LAK / CD16 / CD25 / 癌治療 / リンパ球移入療法 / NK-LAK細胞 / 固相化CD3抗体 / 固相化ガンマグロブリン / CD16抗原 / CD25抗原 / AB型血清 / 肝転移 / 接着分子 / 癌細胞株 / 大腸癌 / 細胞株 / 初代培養
Research Abstract

We have attempted to treat 11 patients with recurrent or metastatic cancer and 2 patients who recieved curative operation, by adoptive transfer of cultured autologous lymphocytes. Among 8 cancer bearing patients who received more than 8x10^9 cells, 6 of them responded at least transiently, including one PR case (case 6) and 2 cases with improved QOL (case 1,11).
Although cells were stimulated with immobilized CD3, highly activated NK cells were expanded in some cultures. NK cells were possively activated by IgG in the culture media, immobilized to the plastic wares during cultivation. In the case 6, large liver metastasis were regressed by combined transfer of highly activated NK cells and CTL,after ethanol injection and local chemotherapy had failed. Since the case was thought to be a good model, we intended to develop a new method for selective NK cell activation using immobilized LgG.NK cells exclusively adhered to the IgG coated ware, and some of them expanded while the others became shrinked or dead. Culture conditions, including co-existence of Mo and T cells, addition of IL2 and/or IL12, were tested. Then, a novel method to overcome activation induced cell death was developed. NK cells from a healthy donor were activated by the method and a NK culture of high purity was obtained expanding 1000 fold. The datails of the method will be reported elsewhere.
NK cells reportedly reach to foci of viral infection at first and may trigger CTL reaction. It might be the case in tumor immunity, provided the patient is not anergy to the tumor antigen. Combined transfer of NK and CTL might bring forward a new strategy for treatment of advanced cancer.

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] 美甘晋介: "固層化CD3抗体刺激を応用したリンパ球移入療法の検討" Biotherapy. 5. 796-798 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S,Mikamo: "Adoptive immunotherapy with fixed-CD3 activated cultured lymphocytes" 日本癌治療学会誌. 27. 101-101 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S,Mikamo: "Adoptive immunotherapy for cancer-bearing patients" Ann.Report 1991 Inst.Med.Sci.Univ.Tokyo. 106-107 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S,Mikamo: "Adoptive immunotherapy for cancer-bearing patients" Ann.Report 1992 Inst.Med.Sci.Univ.Tokyo. 120-121 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S,Mikamo: "Cell transfer therapy of cancer metastasis" Ann.Report 1993 Inst.Med.Sci.Univ.Tokyo. 128-128 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S,Mikamo: "Cell transfer therapy with cultured lymphocytes" Ann.Report 1994 Inst.Med.Sci.Univ.Tokyo. 129-130 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo: "Cell transfer therapy with cultured lymphocytes" Ann.Report 1995 Inst.Med.Sci.Univ.Tokyo. 180-181 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo: "Expansion of pure human NK cells by stimulation with ionmobilized IgG" Ann.Report 1996 Inst.Med.Sci.Univ.Tokyo. 198-198 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 美甘晋介: "リンパ球移入療法-固相化CD3抗体刺激法の応用" HUMAN CELL. 5. 256-266 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekiguchi: "Adoptive immunotherapy of cancer patients with anti-CD3 activated autologous lymphocytes" Recent Advances in Life Sciences. 17-32 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo: "Adoptive immunotherapy with regional environmental modification" Biotherapy. 7. 874-876 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo: "Cell transfer therapy of cancer metastasis with autologous lymphocytes" Cell Transplantation. 4. S65-S67 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 美甘晋介: "ヒトリンパ球の大量培養法" 細胞工学. 14. 223-227 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 美甘晋介: "固相化IgGを用いたヒトNK細胞の選択的活性化法の検討" 日本免疫学会総会・学術集会記録. 26. 283-283 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 美甘晋介(分担執筆): "分子医科学実験プロトコール(2-2-3ヒトリンパ球の大量培養法 PP,202-208)" 秀潤社, 312 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo et al.: "Application of adoptive transfer of cultured lymphocytes stimulated with fixed CD3 antibody." Biotherapy. 5(5). 796-798 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo et al.: "Adoptive immunotherapy for cancer with fixed-CD3 activated cultured lymphocytes." The Journal of Japan Society for Cancer Therapy. 27(2). 101 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo and T.yoneto.: "Adoptive immunotherapy for cancer-bearing patients." Annual Reprt 1991 Inst.Med.Sci.Univ.Tokyo. 106-107 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo et al.: "Adoptive immunotherapy for cancer-bearing patients." Annual RUnleprt 1992 Inst.Med.Sci.Univ.Tokyo. 120-121 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo et al.: "Cell transfer therapy of cancer metastasis." Annual Reprt 1993 Inst.Med.Sci.Univ.Tokyo. 128 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Cell transfer therapy with cultured lymphocytes." Annual Reprt 1994 Inst.Med.Sci.Univ.Tokyo. 129-130 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Cell transfer therapy with cultured lymphocytes." Annual Reprt 1995 Inst.Med.Sci.Univ.Tokyo. 180-181 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Expansion of pure human NK cells by stimulation with immobilized IgG." Annual Reprt 1996 Inst.Med.Sci.Univ.Tokyo. 198 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Adoptive immunotherapy using immobilized anti-CD3 mAb-activated autologous lymphocytes." Human Cell. 5(3). 256-266 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Sekiguchi and S.Mikamo.: "Adoptive immunotherapy of cancer patients with anti-CD3 activated autologous lymphocytes." Recent Advances in Life Sciences. 17-32 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo et al.: "Adoptive immunotherapy with regional environmental modification." Biotherapy. 7(5). 874-876 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Cell transfer therapy of cancer metastasis with autologous lymphocytes." Cell Transplantation. 4(Suppl 1). S65-S67 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Bulk culture of human lymphocytes." Cell Technology. 14(2). 223-227 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo.: "Developement of selective activation method for human NK cells." Proceedings of Japanese Society for Immunology. 26. 283 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] S.Mikamo: Bulk culture of human lymphocytes Cell Technology suppl. [ISBN4-87962-152-8 C3345]. SHUJUNSHA CO., Ltd., Tokyo, 202-208 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Morimasa Sekiguchi: "Adoptive immunotherapy of cancer patients with anti-CD3 activated autologous lymphocytes" RECENT ADVANCES IN LIFE SCIENCES. 17-32 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 美甘晋介: "局所環境を重視したリンパ球移入療法" BIOTHERAPY. 7. 874-876 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shinsuke Mikamo: "Adoptive immunotherapy for cancer-bearing patients" Ann Rep 1992 Ins Med Sci Univ Tokyo. 120-121 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 美甘晋介: "リンパ球移入療法-固相化CD3抗体刺激法の応用-" HUMAN CELL. 5. 256-266 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shinsuke Mikamo: "Adoptive immunotherapy for cancer with fixed-CD3 activated cultured lymphocytes" J Jpn Soc Cancer Ther. 27. 211-211 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 美甘晋介: "固層化CD3抗体刺激を応用したリンパ球移入療法の検討" BIOTHERAPY. 5. 796-798 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] 美甘 晋介: "固層化CD3抗体刺激を応用したリンパ球移入療法の検討" BIOTHERAPY. 5. 796-798 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 美甘 晋介: "リンパ球移入療法ー固相化CD3抗体刺激法の応用ー" HUMAN CELL. 5. 256-266 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 美甘 晋介: "局所環境を重視したリンパ球移入療法" BIOTHERAPY. 7(5). (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shinsuke Mikamo: "Adoptive immunotherapy for cancer with fixed-CD3 activated cultured lymphocytes" The Journal of Japan Soeiety for Cancer Therapy. 27. 211-211 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shinsuke Mikamo: "Adoptive immunotherapy for cancer-bearing patients" Annual Report 1991.The Institute of Medical Science,The University of Tokyo. 106-107 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Shinsuke Mikamo: "Adoptive immunotherapy for cancer-bearing patients" Annual Report 1992.The Institute of Medical Science,The University of Tokyo(tn press). (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 美甘 晋介: "固層化CD3抗体刺激を応用したリンパ球移入療法の検討" BIOTHERAPY. 5. 796-798 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 美甘 晋介: "局所環境を重視したリンパ球移入療法" BIOTHERAPY. (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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