Oncolytic virotherapy for malignant glioma: translating laboratory insights into clinical practice.
Oncolytic virotherapy for malignant glioma: translating laboratory insights into clinical practice.
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DOI：
10.3389/fonc.2013.00032
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发表时间：
2013
影响因子：
4.7
通讯作者：
Lesniak MS
中科院分区：
文献类型：
--
作者：
Auffinger B;Ahmed AU;Lesniak MS
多形性胶质母细胞瘤是成人中最常见和最具侵袭性的脑肿瘤之一，对目前可用的治疗方法具有高度耐药性，并且经常复发。由于其预后差，治疗困难，迫切需要开发新的抗胶质瘤治疗方法并将其转化为临床。在这种情况下，溶瘤病毒疗法成为胶质瘤患者的一种令人兴奋的治疗选择。这些天然或基因工程病毒能够有效地感染癌细胞，诱导特定的抗肿瘤细胞毒作用。此外，一些病毒已被重新设计以调节胶质瘤微环境，表达细胞因子以增强全身抗胶质瘤免疫反应，并结合血管抑制基因以减少胶质瘤血管。尽管最近的临床试验已经证实了脑溶瘤病毒疗法的安全性，但其中等临床疗效尚未达到令人鼓舞的临床前实验室结果。在这篇综述中，我们将讨论目前处于临床前和临床评估阶段的主要抗胶质瘤病毒治疗方法。我们还将回顾不同的递送方法，体内病毒行为，命运，复制，肿瘤内扩散，抗肿瘤免疫反应的激活，以及胶质瘤干细胞的靶向。我们将重点讨论每种治疗方法的优点和局限性，以及如何克服这些障碍，将令人兴奋的实验室结果有效地转化为有希望的临床试验。
Glioblastoma multiforme, one of the most common and aggressive brain tumors in adults, is highly resistant to currently available therapies and often recurs. Due to its poor prognosis and difficult management, there is an urgent need for the development and translation of new anti-glioma therapeutic approaches into the clinic. In this context, oncolytic virotherapy arises as an exciting treatment option for glioma patients. These natural or genetically engineered viruses are able to effectively infect cancer cells, inducing a specific anti-tumor cytotoxic effect. In addition, some viruses have been redesigned to modulate glioma microenvironment, to express cytokines to boost a systemic anti-glioma immune response and to incorporate angiostatic genes to decrease glioma vasculature. Although recent clinical trials have confirmed the safety of oncolytic virotherapies in the brain, their moderate clinical efficacy has not yet matched the encouraging preclinical laboratory results. In this review, we will discuss the leading anti-glioma virotherapy approaches that are presently under preclinical and clinical evaluation. We will also review different delivery methods, in vivo virus behavior, fate, replication, intratumoral spread, activation of anti-tumor immune response, and targeting of glioma stem cells. We will focus on the advantages and limitations of each therapeutic approach and how to overcome these hurdles to effectively translate exciting laboratory results into promising clinical trials.