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病灶内注入淋巴因子激活的杀伤细胞(LAK)和重组白细胞介素-2(rIL-2)用于治疗恶性脑肿瘤患者。

Intralesional infusion of lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2) for the treatment of patients with malignant brain tumor.

作者信息

Merchant R E, Merchant L H, Cook S H, McVicar D W, Young H F

机构信息

Department of Anatomy, Virginia Commonwealth University, Medical College of Virginia, Richmond.

出版信息

Neurosurgery. 1988 Dec;23(6):725-32. doi: 10.1227/00006123-198812000-00007.

Abstract

Twenty patients with supratentorial, intracerebral lesions defined by computed tomographic scan or magnetic resonance imaging were treated by surgery and adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant Interleukin-2 (rIL-2, Cetus). Seventeen patients had glioblastoma, two had high-grade oligodendroglioma, and one patient had two metastatic sarcoma lesions. LAK cells were produced from blood mononuclear cells (MNC) obtained by 2 to 3 leukapheresis procedures and cultured (2.5 x 10(6) MNC/ml) 3 to 5 days with 1000 units rIL-2/ml. Although LAK cells could be produced from MNC of all patients, those taking steroids or with a low Karnofsky functional status generated, on average, suboptimal LAK cell activity. Age, sex, and serum anticonvulsant levels do not seem to influence a patient's ability to produce LAK cells in vitro. For therapy, cultured MNC (1-15 x 10(9] containing LAK cells were suspended in saline containing 10(6) units rIL-2 and injected into tissue surrounding the tumor cavity during craniotomy. For 3 days after their operations, patients received 10(6) units rIL-2 into the tumor cavity through an Ommaya reservoir. The treatment protocol was tolerated well by all patients, although they all experienced some degree of headache, fever, or lethargy that cleared within a few days of the last rIL-2 injection. When computed tomographic (CT) scans were obtained soon after treatment, areas of low density suggested a greater-than-normal extent of edema around the operative site. At the present time, CT scans indicate that the tumors of seven patients have recurred with an average disease-free interval of 25 +/- 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

通过计算机断层扫描或磁共振成像确诊的20例幕上脑内病变患者接受了手术治疗,并采用淋巴因子激活的杀伤细胞(LAK细胞)和重组白细胞介素-2(rIL-2,Cetus公司生产)进行过继性免疫治疗。17例患者患有胶质母细胞瘤,2例患有高级别少突胶质细胞瘤,1例患者有两处转移性肉瘤病灶。LAK细胞由通过2至3次白细胞单采程序获得的血液单核细胞(MNC)产生,并在含1000单位rIL-2/毫升的条件下培养(2.5×10⁶个MNC/毫升)3至5天。虽然所有患者的MNC均可产生LAK细胞,但服用类固醇或卡诺夫斯基功能状态较低的患者平均产生的LAK细胞活性欠佳。年龄、性别和血清抗惊厥药水平似乎不影响患者体外产生LAK细胞的能力。治疗时,将含有LAK细胞的培养MNC(1 - 15×10⁹)悬浮于含10⁶单位rIL-2的盐水中,在开颅手术期间注入肿瘤腔周围组织。术后3天,患者通过Ommaya储液器将10⁶单位rIL-2注入肿瘤腔。所有患者对治疗方案耐受性良好,尽管他们均经历了一定程度的头痛、发热或嗜睡,这些症状在最后一次注射rIL-2后的几天内消退。治疗后不久进行计算机断层扫描(CT)时,低密度区域提示手术部位周围水肿程度高于正常。目前,CT扫描显示7例患者的肿瘤复发,平均无病间期为25±6周。(摘要截取自250字)

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