Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors
Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors
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DOI：
10.1038/nm1297-1362
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发表时间：
1997-12-01
期刊：
影响因子：
82.9
通讯作者：
Oldfield, EH
中科院分区：
文献类型：
--
作者：
Laske, DW;Youle, RJ;Oldfield, EH
我们研究了转铁蛋白-CRM107对复发性恶性脑肿瘤的局部治疗，转铁蛋白是人转铁蛋白（Tf）和白喉毒素基因突变体（CRM107）的结合物，缺乏天然毒素结合。高流量间质微输注绕过了向肿瘤和周围浸润脑输送蛋白质的生理障碍。15例可评估的患者中有9例（60%）在磁共振成像（MRI）上肿瘤体积至少缩小50%，包括2例完全缓解。在治疗1-4周后，3名患者中有3名在1.0 μ g/ml浓度下出现肿瘤周围毒性，但在较低浓度下治疗的9名患者中没有出现。无症状性全身毒性发生。在常规治疗难治性恶性脑肿瘤患者中，局部灌注Tf-CRM107产生肿瘤应答而无全身毒性。直接间质输注可以成功地将大蛋白分布在肿瘤内并浸润肿瘤周围的大脑。
We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1-4 weeks after treatment in three of three patients at 1.0 mu g/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor.