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Cooperative effects between chemotherapy and adoptive immunotherapy for brain tumors

Research Project

Project/Area Number 61570698
Research Category

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

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionOsaka University

Principal Investigator

YOSHIMINE Toshiki (1987)  Osaka University, School of Medicine, Assistant Professor, 医学部, 助手 (00201046)

生塩 之敬  大阪大学, 医学部, 助手 (20028583)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Keiji  Osaka university, School of Medicine, Assistant Professor, 医学部, 助手 (50162699)
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsBrain neoplasms / Lymphokine-activated Killer (LAK) cells / Adoptive immunotherapy / インターロイキシー2 / グリオーマ / Lymphokine-activated killer(LAK)細胞 / インターロイキン-2 / ガンマ・インターフェロン / モデル
Research Abstract

Despite combined treatment with surgery, radiation and chemotherapy, the prognosis of patients with glioblastoma multiforme is very poor. Their median survival time (MST) is 10-12 months. Our in vitro studies showed that peripheral blood lymphocytes, which were activated with human recombinant interleukin-2 (rIL-2), were lytic for autologous or homologous cells but not foro normal lymphocytes or lymphoblasts. The adoptive transfer of these lymphokine-activated killer (LAK) cells had been used in treating twenty-four patients in whom standard therapy had failed: 8 medulloblastoma, 6 glioblastoma multiforme, 4 anaplastic astrocytoma, 2 pineal tumors, 2 metastatic tumors, 1 astrocytoma (grade 2), and 1 pontine tumor. Patients received either 2-15 x10^9 autologous or homologous LAK cells. Two to 30 x 10^8 LAK cells were administered to the patients with brain tumors through Ommaya reservoir or ventriculo-peritoneal shunt valves 2-3 times a week. Twenty-five to 50 units of rIL-2 were given with LAK cells intrathecally during the adoptive immunotherapy. 11 cases had partial responses for this adoptive immunotherapy: the mean remission period was 9.6 months. Complete tumor regression occurred in one patient with meningeal carcinomatosis derived from epipharyngeal cancer and has been sustained 34 months after this adoptive immunotherapy. A six-year-old by with meningeal dissemination from medulloblastoma has been free of disease during 21 months after this treatment. Malignant tumor ceells were eradicated from their cerebrospinal fluid in seven of twelve patients with meningeal dissemination. Eleven of 24 patients wer also effective in reducing the clinical symptoms and signs. Thus, this therapy is an attractive approach for the treatment of malignant brain tumors that are insensitive to several anti-cancer agents.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] 岡本裕: 脳と神経. 38. 233-237 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 清水恵司: 脳と神経. 38. 265-271 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 清水恵司: 日本癌治療学会誌. 21. 760-766 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 岡本裕: 脳と神経. 38. 593-598 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 宮尾泰慶: 癌と化学療法. 13. 2600-2605 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tatsuo Yoshida: Br J Cancer. 53. 773-777 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tatsuo Yoshida: J Neurosurg. 65. 503-507 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 岡本裕: 医学のあゆみ. 140. 833-834 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 宮尾泰慶: 医学のあゆみ. 141. 1015-10161 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 岡本裕: 臨床免疫. 19. 687-694 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Keiji Shimizu: J Neurosurg. 66. 519-521 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yutaka Okamoto: Acra Neurochirurgica(Wien). (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Keiji Shimizu(eds.M.Chatel et al.): "Brain Oncology" Martinus Nijhoff Publishers(Netherlands), 451 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Okamoto, Yutaka, et al:"The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) Cells induced by recombinant IL-2" Brain and Nerve (Tokyo). 38. 233-237 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shimizu, Keiji, et al: "The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma" Brain and Nerve (Tokyo). 38. 265-271 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shimizu, Keiji, et al: "The antitumor efficacy of lymphokine-activated killer (LAK) cells and gamma interferone production induced in vitro from pheripheral blood lymphocytes of patients with malignant glioma" The journal of Japan Society for cancer therapy. 21. 760-766 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Okamoto, Yutaka, et al: "Clinical studies of adoptive immunotherapy of human disseminated brain tumors with LAK cells and recombinant interleukin-2" Brain and Nerve (Tokyo). 38. 593-598 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Miyao, Yasuyoshi, et al: "Meningeal gliomatosis model in nude mice" Jpn J Cancer Chemother.13. 2600-2605 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshida, Tetsuo, et al: "Enhanced effect of reserpine upon growth-inhibitory action of ACNU on ACNU-resistant C_6 glioma" Br J Cancer. 53. 773-777 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Yoshida, Tatsuo, et al: "Development of experimental Meningeal gliomatosis models in rats" J Neurosurg. 65. 503-507 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Okamoto, Yutaka, et al: "Adoptive transfer of allogeneic LAK cells into a patient with medulloblastoma" Igaku no Ayumi. 140. 833-834 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Miyao, Yasuyoshi, et al: "Distribution of lymphokine-activated killer cells in the cerebrospinal space,-Assessment of Indium-111-labeled LAK cell scintigram-" Igaku no Ayumi. 141. 1015-1016 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Okamoto, Yutaka, et al: "Adoptive transfer of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) into 5 patients with meningeal dissemination from malignant tumors" Clin. Immunol.19. 687-694 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shimizu, Keiji, et al: "Adoptive immunotherapy of human meningeal gliomatosis and carcinomatosis with LAK cells and recombinant interleukin-2" J Neurosurg. 66. 519-521 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Okamoto, Yutaka, et al: "An adoptive immunotherapy of patients with medulloblastoma by LAK cells" Acta Neurochirurgica (Wien). (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Shimizu, Keiji, et al (eds. M. Chatel et al): Brain Oncology. Martinus Nijhoff Publishers (Netherlands), 439-443 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 岡本裕: 脳と神経. 38. 233-237 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 清水惠司: 脳と神経. 38. 265-271 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 清水惠司: 日本癌治療学会誌. 21. 760-766 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 岡本裕: 脳と神経. 38. 593-598 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 宮尾泰慶: 癌と化学療法. 13. 2600-2605 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] SHIMIZU,Keiji: Journal of Neurosurgery. 66. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] SHIMIZU,Keiji: "BRAIN ONCOLOGY-Biology,Diagnosis and Therapy" MARTINUS NIJHOFF/DR W.JUNK PUBLISHERS, (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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