Oncolytic Measles Virus Retargeting by Ligand Display

Oncolytic Measles Virus Retargeting by Ligand Display
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DOI:
10.1007/978-1-61779-340-0_11
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发表时间:
2012-01-01
期刊:
ONCOLYTIC VIRUSES: METHODS AND PROTOCOLS
影响因子:
--
通讯作者:
Galanis, Evanthia
Galanis, Evanthia
中科院分区:
其他
文献类型:
--
作者:
Msaouel, Pavlos;Iankov, Ianko D.;Galanis, Evanthia

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尽管近年来取得了重大进展,但转移性恶性肿瘤的治疗仍然是一个重大挑战。迫切需要开发新的治疗方法。病毒治疗方法具有相当大的潜力,其中麻疹病毒(MV)疫苗株已成为一个有前途的溶瘤平台。来自Edmonston疫苗谱系的重靶向MV菌株(MV- edm)对表达受体的肿瘤细胞的抗肿瘤效果与未经修饰的菌株相当,治疗指数更高。在这里,我们描述了完全重靶向的MV-Edm衍生物的构建、修复、扩增和滴定,这些衍生物在病毒表面显示肿瘤特异性受体结合配体,结合H蛋白CD46和SLAM进入消融突变。
Despite significant advances in recent years, treatment of metastatic malignancies remains a significant challenge. There is an urgent need for development of novel therapeutic approaches. Virotherapy approaches have considerable potential, and among them measles virus (MV) vaccine strains have emerged as a promising oncolytic platform. Retargeted MV strains deriving from the Edmonston vaccine lineage (MV-Edm) have shown comparable antitumor efficacy to unmodified strains against receptor expressing tumor cells with improved therapeutic index. Here, we describe the construction, rescue, amplification, and titration of fully retargeted MV-Edm derivatives displaying tumor specific receptor binding ligands on the viral surface in combination with H protein CD46 and SLAM entry ablating mutations.