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Basic and clinical studies on induction of killer lymphocytes against neck and kidney tumors

Research Project

Project/Area Number 01480383
Research Category

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

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionFaculty of Medicine, University of the Ryukyus

Principal Investigator

TANABE Masao J  University of the Ryukyus, Bacteriology, Associate Prof., 医学部(細菌学), 助教授 (30049077)

Co-Investigator(Kenkyū-buntansha) KOJA Shizuo  University of the Ryukyus, Otorhinolaryngology, Lecture, 医学部(耳鼻咽喉科学), 助手 (60161923)
HAYAKAWA Masamichi  University of the Ryukyus, Urology, Associate Prof., 医学部(泌尿器科学), 助教授 (00095639)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1990: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1989: ¥3,600,000 (Direct Cost: ¥3,600,000)
KeywordsAdoptive immuno therapy / LAK(Lymphokine Activated Killer) / TIL(Tumor Infiltrating Lymphocytes) / CTL(Cytotoxic T Lymphocytes) / X-chromosome / Self-nonself discrimination / TSTA(Tumor Specific Transplantation Antigen) / Bone marrow cells / サイトカイン / 腎癌治療 / マイナ-組織適合抗原 / CTL / X染色体(遺伝子産物Xir) / Xー染色体遺伝子産物 / 自己・非自己識別物質 / 腫瘍特異的抗原 / 腎・頭頚部腫瘍 / X染色体遺伝子産物
Research Abstract

This study was made to develop the effective immune therapy for the tumors basing on the results of both basic and clinical researches concerning the induction of killer lymphocytes against neck and kidney tumors. As the clinical trials, Hayakawa M.D. tried to treat the patients with advanced renal cancer with the adoptive transfer of Lymphokine-activated killer (LAK) cells. He developed the regional arterial infusion therapy which yielded the excellent clinical results.
On the other hand, in the basic approach, Tanabe M.D. and Koja M.D. developed the new method for the induction of the cytotoxic T lymphocytes (CTL) against the tumor cells. They also showed in this new system that the CTL recognized only the absolute dominant antigen which had the important role on the immunological self-nonself discrimination.
(Basic approach)
1. The bone marrow (BM) cells had the helper activity which augmented to induce the CTL from their precursors.
2. Using the BM cells which had the helper effect, th … More e CTL specific to the minor-H antigen were induced easily in primary cultures in vitro. By the genetic analysis, the CTL recognized only the X-chromosome linked gene product (Xir) antigen) which had the important role on the self-nonself discrimination.
3. Using the BM cells, the CTL specific to the tumor cells were induced easily in primary cultures in vitro. By the analysis of the rumor antigen recognized by these CTL, the tumor cells had lost the intrinsic Xir antigen which were expressed on normal original cells as described above. On the contrary, the tumor cells gained the new intrinsic Xir-like antigen on their surfaces.
(Clinical approach)
LAK cells and tumor infiltrating lymphocytes (TIL) were obtained from patients with advanced renal cell carcinoma (RCC). Those killer cells-mediated cytotoxicities against autologous tumor cell were nonspecific. Therefore, when they were systemically infused, they rarely reached metastatic sites of RCC. In contrast, regional arterial administration yielded a remarkable accumulation of killer cells in the tumor tissue and they stayed there for a certain period of time. LAK cell and TIL produced IFN-alpha and/or TNF-gamma when they were cultured with autologous tumor cells. The positive rate of these cytokines in the serum of the patients treated with LAK/IL-2 therapy was higher than that in the patients without LAK/IL-2 therapy. Seven out of 12 metastatic lesions in 12 patients with RCC treated with LAK/IL-2 therapy showed regression, whereas no clinical response was obtained with systemic LAK/IL-2 therapy. Regional arterial administration of killer cells seems to be worthwhile and promising for treatment of the advanced RCC as far as the mass production of the specific CTL to RCC is not presently available. Less

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 田辺 将夫: "免疫における自己・非自己識別機構の研究" 西日泌尿誌. 53. 317-324 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanabe,M.J.: "Prethymic nylon wool-passed bone marrow cells,substituing for helper T cells,can augment the generation of cytotoxic T lymphocytes from their precursors." Microbiol.Immunol.35. 1115-1130 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Tanabe,M.J.: "Thy l^- bone marrow cells passed through nylon wool can augment the generation of cytotoxic T lymphocytes(CTL) with preference for the X-chromosome-linked gene product in primary cultures in vitro." Microbiol.Immunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Koja,S.and Tanabe,M.J.: "P815 tumor cells express an intrinsic absolute dominant tumor specific transplantation antigen(TSTA) that functions in immune regulation." Microbiol.Immunol(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 早川 正道他5名: "腎腺癌に対するTIL療法の検討-OKT-3抗体を用いたTILの増殖法" 日泌尿会誌. 81. 103-109 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 早川 正道他4名: "腎癌に対する免疫療法の進歩と問題点" 西日泌尿. 53. 325-334 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masao J. Tanabe: "Study of the mechanisms of immunological self-nonself discriminaion." Nishinihon J. Urol. Vol. 53. 317-324 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masao J. Tanabe: "Prethymic nylon wool-passed bone marrow cells, substituting for helper T cells, can augment the generation of cytotoxic T lymphocytes from their precursors." Microbiol. Immunol.35. 1115-1130 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masao J. Tanabe: "Thy 1^-bone marrow cells passed through nylon wool can augment the generation of cytotoxic T lymphocytes (CTL) with preference for the X-chromosome-linked gene product in primary cultures in vitro." Microbiol. Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Shinzo Koja and Masao J. Tanabe: "P815 tumor cells express an intrinsic absolute dominant tumor specific transplantation antigen (TSTA) that functions in immune regulation." Microbiol. Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masamichi Hayakawa: "Study of adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) for renal carcinoma. - Amplification of IL-2-elicited TIL proliferation by OKT3- monoclonal antibody -" Jpn. J. Urol.Vol. 81. 103-109 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masamichi Hayakawa: "Immunotherapy for renal cell carcinoma: its evolution and its future." Nishinihon J. Urol.Vol. 53. 325-334 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masamichi Hayakawa: "Lymphokine-activated killer traffic assay and our preliminary clinical results of regional arterial infusion of lymphokine-activated killer cells for renal cell carcinoma." Urol. Int.47(suppl). 127-131 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Masamichi Hayakawa: "Lymphokine-activated killer (LAK) therapy for advanced renal cell carcinoma: clinical study on arterial LAK therapy and experimental study on LAK cell activity." Acta Urol Jpn.Vol. 38. 1311-1318 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] M.Hayakawa.,Y.Koyama.,R.D.Williams.and A.Osawa: "Lymphokineーactivated killer traffic assay and our preliminary clinical results of regional arterial infusion of lymphokineーactivated killer cells for renal cell carcinoma" Urologica Internationalis. 47. 127-131 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 早川 正道,秦野 直,比嘉 功,小山 雄三,大澤 炯: "腎癌に対する免疫療法の進歩と問題点" 西日本泌尿器科. 53. 325-334 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 早川 正道: "進行性腎癌に対するLAK療法ー臨床成績とLAK療法に関する基礎的検討ー" 泌尿器科紀要. 38. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.J.Tanabe: "Prethymic nylon woolーpassed bone marrow cells,substitutings for T helper cells,can augment the generation of cytotoxic T lymphocytes from thier precursors." Microbiol,Immunol.35. 1115-1130 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 田辺 将夫: "免疫における自己・非自己識別機構の研究" 西日本泌尿器科. 53. 317-324 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] M.J.Tanabe: "Helper effect by the immune lymphocytes in the bone marrow cells" Microbiol.Immunol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.J.Tanabe: "Induction of the cytotoxic T lymphocytes which have the specificity to minor antigen restricted to allo MHC." Microbiol.Immunol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] S.Kojya & M.J.Tanabe: "Induction of the cytotoxic T lymphocytes which have the specificity to tumor specificic transplantation antigens." Microbiol.Immunol.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 田辺 将夫: "自己・非自己識別機構の研究" 西日本泌尿器科学雑誌. (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.HAYAKAWA;A.OSAWA;T.HATANO: "Effects of metastatic renal cell carcinoma of regional arterial and direct intratumor administration of lymphokineーactivated killer cells in combination with systemic interleukinー2." Immunotherapy of Urological Tumors.213-218 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.HAYAKAWA;Y.KOYAMA;R.D.WILLIAMS: "LymphokineーActivated Killer Traffic Assay and Our Preliminary Clinical Results of Regional Arterial Infusion of Lymphokineーactivated killer cells for Renal cell Carcinoma." Urological internationals.(1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] M.J.Tanabe: "Helper effect by the immature lymphocytes in the bone marrow cells" Microbiol.Immunol.

    • Related Report
      1989 Annual Research Report
  • [Publications] M.J.Tanabe: "Induction of the cytotoxic T lymphocytes which have the specificity to minor antigen restricted to allo MHC" Microbiol.Immunol.

    • Related Report
      1989 Annual Research Report
  • [Publications] 早川正道: "腎腺癌に対するTIL療法の検討ーOKT-3抗体を用いたTILの増殖法" 日本泌尿器科学会雑誌. 81. 103-109 (1990)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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