Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies.
Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies.
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对流增强 IL13-PE38QQR 递送治疗复发性恶性神经胶质瘤：介绍正在进行的 1 期研究的中期结果。
DOI：
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
S. Kunwar
中科院分区：
文献类型：
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作者：
S. Kunwar
IL 13 PE 38 QQR是由假单胞菌外毒素A的酶活性部分与人IL 13缀合组成的重组毒素。IL 13-PE 38与IL 13受体（IL 13 R）的结合允许重组毒素的内化，导致在纳摩尔浓度下的选择性和有效的细胞毒性。正常脑组织表达很少或不表达IL 13 R，但恶性胶质瘤过度表达IL 13 R，从而赋予该试剂选择性细胞毒性。对流增强递送（CED）是一种新型的直接药物递送方法，用于肿瘤和肿瘤周围区域，使用正压输注产生压力梯度，优化大分子在脑内的分布。已经启动了三项I期研究以研究IL 13-PE 38 QQR作为用于治疗复发性恶性胶质瘤患者的抗肿瘤剂。截至2003年1月，共有46名病人接受了治疗。在2003年3月神经胶质瘤EANS局部治疗会议上的报告反映了截至2003年1月的不良事件发现和截至2003年3月的生存数据。肿瘤内灌注联合或不联合切除术在皮质类固醇预防治疗下耐受性良好，尤其是对于颅内压升高的患者。切除术后灌注到瘤周脑实质中似乎也耐受良好。在0.5-2.0 μ g/mL的药物浓度下观察到组织学肿瘤效应。虽然I期研究不关注疗效评价，但在这一选定患者人群中观察到生存时间延长。临床前数据和细节和三个临床试验的初步结果进行了审查。
IL13PE38QQR is a recombinant toxin composed of the enzymatically-active portion of Pseudomonas Exotoxin A conjugated with human IL13. Binding of IL13-PE38 to the IL13 receptor (IL13R) permits internalization of the recombinant toxin resulting in selective and potent cytoxicity at nanomolar concentrations. Normal brain tissue expresses little or no IL13R, but malignant gliomas overexpress IL13R conferring the selective cytotoxicity to the agent. Convection-enhanced delivery (CED), a novel direct drug delivery method to tumor and peritumoral region uses positive pressure infusion to generate a pressure gradient that optimizes distribution of macromolecules within the brain. Three phase I studies have been initiated to investigate IL13-PE38QQR as an anti-tumor agent for the treatment of patients with recurrent malignant gliomas. As of January 2003 a total of 46 patients have been treated. The presentation at the March 2003 EANS Local Therapy of Glioma meeting reflects adverse event findings through January 2003 and survival data through March 2003. Intratumoral infusion with or without resection is fairly well-tolerated with corticosteroids prophylaxis particularly for patients with raised intracranial pressure. Post-resection infusion into the peritumoral brain parenchyma also appears to be very well tolerated. Histopathological tumor effect was seen at drug concentrations of 0.5-2.0 microg/mL. Although phase I studies do not focus on efficacy evaluation, prolonged survival times have been observed in this select population of patients. The preclinical data and details and preliminary results of the three clinical trials are reviewed.
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DOI：
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发表时间：
1999-05
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
W. Debinski;D. Gibo;S. W. Hulet;J. Connor;G. Gillespie
通讯作者：
W. Debinski;D. Gibo;S. W. Hulet;J. Connor;G. Gillespie
使用正压输注在大脑中分布大分子染料：治疗剂直接控制输送的模型。
影响因子：
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作者：
Prabhu,SS;Broaddus,WC;Gillies,GT;Loudon,WG;Chen,ZJ;Smith,B
通讯作者：
Smith,B
影响因子：
4.1
作者：
Chen, MY;Lonser, RR;Oldfield, EH
通讯作者：
Oldfield, EH
影响因子：
4.4
作者：
B. Bochner;David Klunk;S. A. Sterbinsky;R. Coffman;R. Schleimer
通讯作者：
B. Bochner;David Klunk;S. A. Sterbinsky;R. Coffman;R. Schleimer