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Systematic Characterization of the Biodistribution of the Oncolytic Virus M1.
Human Gene Therapy ( IF 3.9 ) Pub Date : 2020-11-13 , DOI: 10.1089/hum.2020.114
Jing Cai 1 , Wenbo Zhu 1 , Yuan Lin 1 , Suzhen Zhang 2 , Xueqing Chen 2 , Shoufang Gong 2 , Songmin He 2 , Jun Hu 1 , Guangmei Yan 1 , Jiankai Liang 1
Affiliation  

Oncolytic viruses are emerging as important tools for immunotherapy for cancer treatment; however, most of the clinically tested oncolytic candidates are still administered by intratumoral injection, and new viruses capable of intravenous injection are urgently needed. The M1 virus is a positive-sense single-stranded RNA virus that belongs to the alphavirus family, and it was identified as an oncolytic virus that can selectively replicate in and kill tumor cells after intravenous injection. To further develop M1 for clinical research through intravenous injection, we systematically investigated the biodistribution characteristics of the M1 virus in normal rats, cynomolgus monkeys, and tumor-bearing immunocompromised mice. The data showed that the M1 virus was eliminated gradually from normal tissue but replicated and increased rapidly in tumor tissue. More importantly, the virus also infiltrated the blood–brain barrier and specifically replicated in and killed malignant glioma in immunocompetent mice. Our data proved the tumor selectivity and safety of the M1 virus, supporting its further clinical development.

中文翻译:

溶瘤病毒 M1 生物分布的系统表征。

溶瘤病毒正在成为癌症治疗免疫疗法的重要工具;然而,大多数临床测试的溶瘤候选药物仍然通过瘤内注射给药,迫切需要能够静脉注射的新病毒。M1病毒是一种正链单链RNA病毒,属于甲病毒科,经鉴定是一种溶瘤病毒,静脉注射后可选择性地在肿瘤细胞内复制并杀死肿瘤细胞。为了通过静脉注射进一步开发用于临床研究的 M1,我们系统地研究了 M1 病毒在正常大鼠、食蟹猴和荷瘤免疫功能低下小鼠中的生物分布特征。数据显示,M1病毒从正常组织中逐渐消除,但在肿瘤组织中迅速复制和增加。更重要的是,该病毒还渗入了血脑屏障,并在免疫活性小鼠的恶性胶质瘤中特异性复制并杀死了恶性胶质瘤。我们的数据证明了 M1 病毒的肿瘤选择性和安全性,支持其进一步的临床开发。
更新日期:2020-11-17
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