Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus
Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus
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DOI：
10.1158/0008-5472.can-12-2221
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发表时间：
2013-01-15
期刊：
影响因子：
11.2
通讯作者：
Buchholz, Christian J.
中科院分区：
文献类型：
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作者：
Bach, Patricia;Abel, Tobias;Buchholz, Christian J.
肿瘤起始细胞（TIC）是开发更有效的抗肿瘤策略的关键但难以回避的靶标。细胞表面标记物 CD133 经常用于识别各种肿瘤实体的 TIC，包括肝细胞癌和胶质母细胞瘤。在这里，我们描述了重新靶向 CD133 的溶瘤麻疹病毒 (MV)。这两种病毒被称为 MV-141.7 和 MV-AC133，感染并选择性裂解 CD133(+) 肿瘤细胞。这两种病毒对非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠皮下或多灶性腹膜腔中生长的人肝细胞癌具有强烈的抗肿瘤作用。值得注意的是，靶向 CD133 的病毒比亲代 MV-NSe 在延长生存方面更有效，后者目前在临床试验中被评估为溶瘤剂。有趣的是，靶受体过度表达或通过肿瘤细胞的扩散动力学增加被排除为 CD133 靶向病毒溶瘤活性增强的原因。 MV-141.7 在原位神经胶质瘤肿瘤球和原发性结肠癌的小鼠模型中也有效。我们的研究结果表明，针对CD133的麻疹病毒选择性地消除肿瘤组织中的CD133(+)细胞，为肿瘤生物学和癌症治疗的研究提供了关键工具。癌症研究； 73(2)； 865-74。 (C) 2013 年 AACR。
Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133(+) tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133(+) cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy. Cancer Res; 73(2); 865-74. (C) 2013 AACR.