Project/Area Number |
61570698
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Cerebral neurosurgery
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Research Institution | Osaka 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)
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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)
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Keywords | Brain 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.
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