Recombinant Chinese Hu191 measles virus exhibits a significant antitumor activity against nephroblastoma mediated by immunogenic form of apoptosis

重组中国 Hu191 麻疹病毒表现出显著的抗肾母细胞瘤活性,该活性通过免疫原性凋亡介导

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作者:Mengying Zhu, Yilong Wang, Chufan Qu, Rongxian Liu, Chudi Zhang, Jinhu Wang, Dongming Zhou, Weizhong Gu, Peichun Chen, Benqing Wu, Zhengyan Zhao

Abstract

In previous studies oncolytic measles viruses (MVs) have shown significant antitumor activity against various tumors. In our research recombinant MV-Hu191 (rMV-Hu191), established via reverse genetics technology and expressing enhanced green fluorescent protein (EGFP), was evaluated for its therapeutic effects and related mechanisms against nephroblastoma cell lines. We built three different constructs based on rMV-Hu191 to express EGFP effectively. Our experiments showed that rMV-Hu191 expressing EGFP could efficiently infect and replicate in nephroblastoma cell lines. Caspase-induced apoptosis exerted a significant impact on MV-induced cell death, which was accompanied by emission of cellular ATP and high-mobility group protein 1 (HMGB1) and by translocation of calreticulin (CRT). Intratumoral injection of rMV-Hu191-EGFP resulted in significant regression of tumors in a G401 xenograft model. Our results indicate that the MV-Hu191 strain, which is widely used in China, is an appropriate vector for expression of foreign genes and could serve as a potentially good candidate for nephroblastoma therapy mediated by induction of apoptosis-associated immunogenic cell death (ICD).

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