Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Neurosurg Rev. 2021 Feb;44(1):29-49. doi: 10.1007/s10143-019-01203-3. Epub 2019 Nov 28.
Malignant glioma, which is characterized by diffuse infiltration into the normal brain parenchyma, is the most aggressive primary brain tumor with dismal prognosis. Over the past 40 years, the median survival has only slightly improved. Therefore, new therapeutic modalities must be developed. In the 1990s, suicide gene therapy began attracting attention for the treatment of malignant glioma. Some clinical trials used a viral vector for suicide gene transduction; however, it was found that viral vectors cannot cover the large invaded area of glioma cells. Interest in this therapy was recently revived because some types of stem cells possess a tumor-tropic migratory capacity, which can be used as cellular delivery vehicles. Immortalized, clonal neural stem cell (NSC) line has been used for patients with recurrent high-grade glioma, which showed safety and efficacy. Embryonic and induced pluripotent stem cells may be considered as sources of NSC because NSC is difficult to harvest, and ethical issues have been raised. Mesenchymal stem cells are alternative candidates for cellular vehicle and are easily harvested from the bone marrow. In addition, a new type of nonlytic, amphotropic retroviral replicating vector encoding suicide gene has shown efficacy in patients with recurrent high-grade glioma in a clinical trial. This replicating viral capacity is another possible candidate as delivery vehicle to tackle gliomas. Herein, we review the concept of suicide gene therapy, as well as recent progress in preclinical and clinical studies in this field.
恶性胶质瘤的特征是向正常脑实质弥漫性浸润，是预后最差的最具侵袭性的原发性脑肿瘤。在过去的 40 年中，中位生存期仅略有改善。因此，必须开发新的治疗方法。在 20 世纪 90 年代，自杀基因治疗开始受到关注，用于治疗恶性胶质瘤。一些临床试验使用病毒载体进行自杀基因转导；然而，发现病毒载体不能覆盖胶质瘤细胞的大面积侵袭区域。由于某些类型的干细胞具有肿瘤趋向性迁移能力，可作为细胞递药载体，因此最近重新引起了人们对这种治疗方法的兴趣。永生化克隆神经干细胞 (NSC) 系已用于复发性高级别胶质瘤患者，显示出安全性和疗效。胚胎和诱导多能干细胞可作为 NSC 的来源，因为 NSC 难以采集，并且引发了伦理问题。间充质干细胞是细胞载体的另一种候选物，可从骨髓中轻易采集。此外，一种新型非溶血性、双嗜性逆转录病毒复制载体，编码自杀基因，在一项临床试验中显示出对复发性高级别胶质瘤患者的疗效。这种复制病毒能力是作为递药载体来治疗脑肿瘤的另一种可能的候选物。本文综述了自杀基因治疗的概念，以及该领域在临床前和临床研究中的最新进展。
