Immunological conditions of patients with malignant gliomas ---Therapeutic drugs and Selection of BRMs---

恶性胶质瘤患者的免疫状况---治疗药物及BRMs的选择---

• 批准号: 62570656
• 负责人: SHIMIZU Keiji
• 金额: $ 1.15万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570656/
• 关键词: Brain neoplasms; Interferons; Anticonvalsants; Immunotherapy; BRM; LAK; 養子免疫療法; インターフェロン; 抗ケイレン剤; IAK

Despite of the combined treatment with surgery, radiation and chemotherapy, the prognosis of patients with glioblastoma multiforme is very poor. Their median survival time (MST) is about 10 months. Therefore, we investigated the immunological condition of some patients with malignant gliomas to search their better therapeutic procedure. The brain tumor patients were examined the production of gamma interferon (IFN-gamma) from their peripheral blood lymphocytes (PBL), which was induced by co-culture with OK-432 for 3 days. The IFNgamma production of healthy subjects and brain tumor patients was 5,367 525 and 198 66 units/ml, respectively. Thus, The IFN production of brain tumor patients was impaired at a relatively early stage (Karnofsky Scale; over 70%) of these disease. ACNU, a kind of some nitrosourea derivatives, induced bone marrow suppression of brain tumor patients. It is possible that these drugs were administered once 6 to 8 weeks. Their in vitro anti-tumor efficacy was showed … More around 40% against malignant glioma cells. Seizures are sometimes the initial symptom of brain tumor patients. It is also indispensable to give them anticonvulsant agents as prophylactic anticonvulsant therapy for a long time. So, we evaluated the effects of three popular anti-convulsants (phenytoin, phenobarbital and valproate) upon the cellmediated immunity, by using normal mice. Phenytoin showed immunosuppression severely. In turn, sodium valproate never suppressed any immunological activity. No anticonvulsant agents suppressed the anti-tumor activity of LAK cells. The adoptive immunotherapy with these LAK cells had been done in twenty-four patients in whom standard therapy had failed. Eleven cases had partial responses for this therapy: the mean remission period was 16 months. The longsurvival with meningeal carcinomatosis derived from epipharyngeal cancer and has been sustained 44 months after this adoptive immunotherapy. Malignant tumor cells were eradicated from their cerebrospinal fluid in seven of twelve patients with meningeal dissemination. Eleven of 24 patients were also effective in reducing the clinical symptoms and signs. Thus, this adoptive immunotherapy is an attractive approach for the treatment of malignant brain tumors that are insensitive to several anti-cancer agents. Less

尽管采用手术、放疗、化疗等综合治疗，但多形性胶质母细胞瘤患者的预后很差。中位生存期（MST）约为10个月。因此，我们对部分恶性胶质瘤患者的免疫状况进行了调查，以寻求更好的治疗方案。检测脑肿瘤患者的外周血淋巴细胞（PBL）产生γ干扰素（IFN-γ）的情况，所述外周血淋巴细胞通过与OK-432共培养3天来诱导。正常人和脑肿瘤患者IFN-γ产生量分别为5367525和19866单位/ml。因此，脑肿瘤患者的IFN产生在这些疾病的相对早期（Karnofsky量表;超过70%）受损。ACNU是一种亚硝基脲类衍生物，可引起脑肿瘤患者骨髓抑制。这些药物可能在6至8周内给药一次。体外抗肿瘤实验表明， ...更多信息 对恶性胶质瘤细胞的杀伤率约为40%。癫痫发作有时是脑肿瘤患者的最初症状。预防性抗惊厥治疗应长期给予抗惊厥药物。因此，我们用正常小鼠评价了三种常用的抗惊厥药物（苯妥英钠、苯巴比妥和丙戊酸钠）对细胞免疫的影响。苯妥英钠显示严重的免疫抑制。反过来，丙戊酸钠从未抑制任何免疫活性。无抗惊厥药物抑制LAK细胞的抗肿瘤活性。这些LAK细胞的过继免疫治疗已经在24例标准治疗失败的患者中完成。11例患者对该疗法有部分反应，平均缓解期为16个月。这种过继性免疫治疗后，来自下咽癌的脑膜癌病的长期生存期已持续44个月。12例脑膜播散患者中有7例从脑脊液中清除了恶性肿瘤细胞。24例患者中有11例在减轻临床症状和体征方面也有效。因此，这种过继免疫疗法是一种有吸引力的方法，用于治疗对几种抗癌药物不敏感的恶性脑肿瘤。少

项目成果

Okamoto,Y.: Cancer Immunol Immunother. 26. 176-179 (1988)

冈本，Y.：癌症免疫免疫疗法。

田村和義: 医学のあゆみ. 147. 289-290 (1988)

田村一义：医学史。147. 289-290 (1988)

朴啓彰: 小児の脳神経.

朴基昌：童年的脑神经。

Shimizu,K.: "Brain oncology" Martinus Nijhoff Publishers, 439-443 (1987)

Shimizu,K.：“脑肿瘤学”Martinus Nijhoff 出版社，439-443 (1987)

Shimizu, Keiji: "Adoptive immunotherapy of human meningeal gliomatosis and carcinomatosis with LAK cells and recombinant interleukin-2" J Neurosurg. 66. 519-521 (1987)

Shimizu, Keiji：“用 LAK 细胞和重组白细胞介素 2 治疗人脑膜胶质瘤病和癌病的过继免疫疗法”J Neurosurg。