Sampson John H, Reardon David A, Friedman Allan H, Friedman Henry S, Coleman R Edward, McLendon Roger E, Pastan Ira, Bigner Darell D
Duke University Medical Center, Durham, NC 27710, USA.
Neuro Oncol. 2005 Jan;7(1):90-6. doi: 10.1215/S1152851703000589.
Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anti-convulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, TP-38.
多形性胶质母细胞瘤对传统治疗仍然难治，因此迫切需要新的治疗方法。TP - 38是一种重组嵌合蛋白，包含一种基因工程形式的细胞毒性绿脓杆菌外毒素，与转化生长因子（TGF）-α融合。TGF -α与表皮生长因子受体具有高亲和力结合，该受体在恶性胶质瘤中普遍过度表达，通常是由于基因扩增。在接受TP - 38治疗之前，此处描述的患者对多种其他治疗完全无效，有肿瘤进展的影像学和病理学证据。治疗后，她临床症状改善，停用了类固醇和抗惊厥药物，增强的肿瘤体积逐渐减小。尽管之前多次复发，但在接受TP - 38治疗后她已超过43个月未进展。残留的小面积强化区域在组织学上无肿瘤证据，在正电子发射断层扫描上代谢减低。本报告描述了一名双侧额叶多形性胶质母细胞瘤患者经瘤内注射新型靶向毒素TP - 38后出现的显著且持续的临床和影像学反应。
