Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38.
Interstitial infusion of glioma-targeted recombinant immunotoxin 8H9scFv-PE38.
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DOI：
10.1158/1535-7163.mct-09-0996
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发表时间：
2010-04
影响因子：
5.7
通讯作者：
Souweidane MM
中科院分区：
文献类型：
--
作者：
Luther N;Cheung NK;Souliopoulos EP;Karampelas I;Bassiri D;Edgar MA;Guo HF;Pastan I;Gutin PH;Souweidane MM
Monoclonal antibodies (MAbs) have the potential to target therapy for high-grade gliomas. MAb 8H9 is specific for membrane protein B7H3 and is reactive with the majority of human high-grade gliomas. We tested the 8H9scFv-PE38 recombinant Pseudomonas-immunotoxin in a preclinical model of high-grade glioma. The IC50 of 8H9scFv-PE38 in vitro was determined using glioblastoma cell lines U87 and U251. Maximum tolerated infusion dose (MTID) of 8H9scFv-PE38 following interstitial infusion to the striatum and pons was defined using athymic rats. MTID of 8H9scFv-PE38 or PBS control were interstitially delivered to athymic rats xenografted with U87 in the striatum or brain stem. Radiographic response and survivals were measured and compared between treatment groups. The in vitro IC50 of 8H9scFv-PE38 for U87 was 1265 ng/ml, and for U251, 91 ng/ml. The MTIDs of interstitially infused 8H9scFv-PE38 to the striatum and brain stem were 0.75 μg and 1.8 μg, respectively. For rats harboring intracranial U87 xenografts, infusion of 8H9scFv-PE38 increased mean survival (striatum: 43.4 days versus 24.6 days; brain stem: 80.6 days versus 45.5 days, n=28 total) and produced 3 long term survivors past 120 days. None of the 14 placebo-treated animals survived longer than 54 days. Tumors also showed volumetric response to infusion of 8H9scFv-PE38 by MRI. Interstitial infusion of 8H9scFv-PE38 shows potential for the treatment of hemispheric and brain stem glioma.
