Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.
Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.
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DOI：
10.1186/1471-2407-12-508
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发表时间：
2012-11-07
期刊：
影响因子：
3.8
通讯作者：
Studebaker AW
中科院分区：
文献类型：
--
作者：
Hutzen B;Pierson CR;Russell SJ;Galanis E;Raffel C;Studebaker AW
髓母细胞瘤是儿童最常见的恶性脑肿瘤。尽管髓母细胞瘤患者的临床结果已显著改善，但患有该疾病的儿童经常遭受与目前可用治疗的侵袭性相关的使人衰弱的副作用。迫切需要用于治疗髓母细胞瘤的替代手段。我们以前已经表明，溶瘤麻疹病毒（MV）可以选择性地靶向和破坏髓母细胞瘤肿瘤细胞的局部和播散模型的疾病。MV-NIS是一种编码人甲状腺钠碘同向转运体（NIS）的溶瘤麻疹病毒，具有向肿瘤部位提供靶向放射治疗的潜力，并促进局部旁观者效应超过单独MV所实现的效应。我们评估了MV-NIS对体外髓母细胞瘤细胞的疗效，并检查了它们在不同时间点掺入放射性碘的能力，发现感染后48小时摄取峰值。MV-NIS的作用也在局部和播散性髓母细胞瘤的小鼠异种移植模型中进行了评价。在无胸腺裸鼠的尾壳核（局部疾病）或右侧脑室（播散性疾病）中注射D283 med-Luc髓母细胞瘤细胞，随后用MV-NIS治疗。这些小鼠的亚组在24、48或72小时后给予131 I剂量。MV-NIS治疗本身以及与131 I联合治疗均可引起治疗小鼠的肿瘤稳定和消退，并显着延长其生存时间。给小鼠注射131 I后，发现放射性碘在肿瘤转移部位聚集。此外，在MV-NIS治疗后24或48小时给予131 I的局部肿瘤小鼠比单独给予MV-NIS的小鼠表现出显著的生存优势。这些数据表明MV-NIS加放射性碘可能是治疗髓母细胞瘤的一种潜在有用的疗法。
Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS), has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease) or right lateral ventricle (disseminated disease) and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for the treatment of medulloblastoma.
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影响因子：
11.5
作者：
Hasegawa, K;Pham, L;Peng, KW
通讯作者：
Peng, KW
DOI：
10.1007/978-1-61779-340-0_11
发表时间：
2012-01-01
期刊：
ONCOLYTIC VIRUSES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Msaouel, Pavlos;Iankov, Ianko D.;Galanis, Evanthia
通讯作者：
Galanis, Evanthia
影响因子：
3.7
作者：
Liu H;Ren G;Miao Z;Zhang X;Tang X;Han P;Gambhir SS;Cheng Z
通讯作者：
Cheng Z
影响因子：
6.7
作者：
Myers, R. M.;Greiner, S. M.;Russell, S. J.
通讯作者：
Russell, S. J.
影响因子：
11.2
作者：
Anderson, BD;Nakamura, T;Peng, KW
通讯作者：
Peng, KW