Department of Oncology, Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Hum Gene Ther. 2012 Apr;23(4):419-27. doi: 10.1089/hum.2011.158. Epub 2012 Mar 9.
Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor activity against glioma lines and orthotopic xenografts; this compares favorably with the MV strain expressing the human carcinoembryonic antigen, which is currently in clinical testing. Expression of NIS protein in infected cells results in effective concentration of radioactive iodine, which allows for in vivo monitoring of localization of MV-NIS infection by measuring uptake of (123)I or (99m)Tc. In addition, radiovirotherapy with MV-NIS followed by (131)I administration resulted in significant increase of MV-NIS antitumor activity as compared with virus alone in both subcutaneous (p=0.0003) and orthotopic (p=0.004) glioblastoma models. In conclusion, MV-NIS-based radiovirotherapy has significant antitumor activity against glioblastoma multiforme and represents a promising candidate for clinical translation.
工程化麻疹病毒（MV）株来源于疫苗株，代表了一种很有前途的溶瘤平台，目前正在进行 I 期临床试验。在这项研究中，我们已经证明，遗传工程表达人钠碘转运体（NIS）的 MV 株对神经胶质瘤系和原位异种移植物具有显著的抗肿瘤活性；这与目前正在临床测试的表达人癌胚抗原的 MV 株相比具有优势。感染细胞中 NIS 蛋白的表达导致放射性碘的有效浓度，从而可以通过测量（123）I 或（99m）Tc 的摄取来监测 MV-NIS 感染的定位。此外，MV-NIS 的放射病毒治疗后再给予（131）I 治疗，与单独使用病毒相比，在皮下（p=0.0003）和原位（p=0.004）胶质母细胞瘤模型中均显著增加了 MV-NIS 的抗肿瘤活性。总之，基于 MV-NIS 的放射病毒治疗对多形性胶质母细胞瘤具有显著的抗肿瘤活性，是临床转化的有前途的候选者。
