Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors
Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors
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DOI：
10.1016/j.gene.2015.04.001
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发表时间：
2015-07-01
期刊：
影响因子：
3.5
通讯作者：
Babovic-Vuksanovic, Dusica
中科院分区：
文献类型：
--
作者：
Deyle, David R.;Escobar, Diana Zarate;Babovic-Vuksanovic, Dusica
恶性周围神经鞘肿瘤（MPNSTs）是一种破坏性的软组织肉瘤，可零星发生或与I型神经纤维瘤病相关，预后差，治疗选择有限。溶瘤麻疹病毒疗法已被证明在许多不同的癌症中具有显著的抗肿瘤特性，但在MPNST上表达人碘化钠同调体（MV- nis）的MVEdm疫苗株的溶瘤潜力尚未得到评估。发现MPNST细胞系在其细胞表面高度表达CD46，这是麻疹病毒进入所需的细胞受体。体外感染MV-NIS后，MPNST细胞系表现出明显的细胞病变效应（CPE），而正常雪旺细胞对CPE的敏感性较低。1-125摄取成像可以监测病毒的定位和分布。将MV-NIS局部注入mpnst源性肿瘤后，肿瘤显著消退，生存率显著提高。这些结果证明了溶瘤麻疹病毒治疗MPNST患者的可行性，以及NF1肿瘤患者的新治疗方法的可能性。(C) 2015 Elsevier B.V.版权所有
Malignant peripheral nerve sheath tumors (MPNSTs) are devastating soft tissue sarcomas that can arise sporadically or in association with neurofibromatosis type I, have a poor prognosis, and have limited treatment options. Oncolytic measles virus therapy has been demonstrated to have significant antitumor properties in a number of different cancers, but the oncolytic potential of a MV Edmonston (MVEdm) vaccine strain engineered to express the human sodium iodide symporter (MV-NIS) on MPNST has not previously been evaluated. MPNST cell lines were found to highly express CD46, a cellular receptor required for measles viral entry, on their cell surface. After in vitro MV-NIS infection, MPNST cell lines showed significant cytopathic effect (CPE), while normal Schwann cells were less susceptible to CPE. Virus localization and distribution could be monitored by imaging of 1-125 uptake. Local administration of MV-NIS into MPNST-derived tumors resulted in significant regression of tumor and improved survival. These results demonstrate feasibility of oncolytic measles virus therapy for MPNST patients and the possibility of a novel treatment for patients with NF1 tumors. (C) 2015 Elsevier B.V. All rights reserved.