Current status of gene therapy for brain tumors.
Current status of gene therapy for brain tumors.
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DOI：
10.1016/j.trsl.2012.11.003
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Rabkin SD
中科院分区：
文献类型：
--
作者：
Murphy AM;Rabkin SD
胶质母细胞瘤（GBM）是成人中最常见和最致命的原发性脑肿瘤，目前的治疗对疾病进展的影响有限。因此，非常需要开发替代治疗方案。基因治疗是一种治疗策略，其依赖于将遗传物质（通常是转基因或病毒）递送到细胞中以用于治疗目的，并且已经越来越有希望地应用于GBM。我们已经在该策略中包括了选择性复制能力的溶瘤病毒，尽管该病毒直接作为复杂的生物抗肿瘤剂而不是作为经典的基因递送载体。GBM是基因治疗的良好候选者，因为肿瘤局部保留在脑内并且很少转移到其他组织;脑中的大多数细胞是有丝分裂后的，这允许特异性靶向分裂的肿瘤细胞;并且肿瘤通常可以通过神经外科手术进行治疗。用于脑肿瘤的递送载体包括非复制病毒载体、正常成体干/祖细胞和溶瘤病毒。治疗性转基因或病毒通常具有细胞毒性或表达激活自杀基因的前药以杀死神经胶质瘤细胞，具有免疫刺激性以诱导或扩增抗肿瘤免疫应答，和/或改变肿瘤微环境，例如阻断血管生成。本文就目前胶质瘤基因治疗的临床前和临床策略作一综述。
Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replication-competent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.
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