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Liposome Encapsulation of Oncolytic Virus M1 To Reduce Immunogenicity and Immune Clearance in Vivo
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2019-01-03 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b01046
Yalong Wang 1 , Huizhi Huang 1 , Haijuan Zou 1, 2 , Xuyan Tian 3 , Jun Hu 3 , Pengxin Qiu 3 , Haiyan Hu 1 , Guangmei Yan 3
Affiliation  

Oncolytic viral therapy is an attractive novel strategy for cancer therapy. As a natural alphavirus, oncolytic virus M1 is able to infect and kill various zinc finger antiviral protein (ZAP)-deficient tumor cells selectively, while leaving normal cells undamaged. However, M1 can trigger the production of neutralizing antibodies that dramatically weaken its antitumor effect. In order to attenuate immunogenicity of the therapeutic M1 virus, we encapsulated it into liposomes (referred to as M-LPO) using the thin-film hydration method. The effect of anti-M1 neutralizing antibody on M-LPO was examined in LoVo and Hep 3B cell lines. In the absence of neutralizing antibodies, treating cells with naked M1, blank liposomes (LPO), M-LPO, or a simple mixture of M1 and liposomes (LPO+M1) inhibited cell growth. In the presence of neutralizing antibodies, only M-LPO inhibited cell growth. After intravenous administration, M-LPO reduced the production of the M1-neutralizing antibody and the corresponding immune response. Analysis of the M-LPO uptake by cells was examined by confocal microscopy using M1 labeled with FITC and liposomal shells labeled with RhB. The results suggest that M1 may be released from liposomes before or after M-LPO internalization. Taken together, our results suggest that encapsulating oncolytic virus M1 in liposomes may reduce intrinsic viral immunogenicity for improved anticancer therapy.

中文翻译:

溶瘤病毒M1的脂质体封装可降低体内免疫原性和免疫清除率

溶瘤病毒疗法是用于癌症疗法的一种有吸引力的新颖策略。作为天然的甲型病毒,溶瘤病毒M1能够选择性感染并杀死各种缺乏锌指抗病毒蛋白(ZAP)的肿瘤细胞,而不会破坏正常细胞。但是,M1可以触发中和抗体的产生,从而大大削弱其抗肿瘤作用。为了减弱治疗性M1病毒的免疫原性,我们使用薄膜水化方法将其封装到脂质体(称为M-LPO)中。在LoVo和Hep 3B细胞系中检查了抗M1中和抗体对M-LPO的作用。在没有中和抗体的情况下,用裸M1,空白脂质体(LPO),M-LPO或M1和脂质体(LPO + M1)的简单混合物处理细胞会抑制细胞生长。在存在中和抗体的情况下,只有M-LPO抑制细胞生长。静脉内给药后,M-LPO减少了M1中和抗体的产生以及相应的免疫反应。通过共聚焦显微镜,使用标记为FITC的M1和标记为RhB的脂质体壳,对细胞摄取M-LPO的分析进行了分析。结果表明,M1可能在M-LPO内化之前或之后从脂质体中释放出来。两者合计,我们的结果表明,将溶瘤病毒M1包裹在脂质体中可能会降低固有的病毒免疫原性,从而改善抗癌治疗。通过共聚焦显微镜,使用标记为FITC的M1和标记为RhB的脂质体壳,对细胞摄取M-LPO的分析进行了分析。结果表明,M1可能在M-LPO内化之前或之后从脂质体中释放出来。两者合计,我们的结果表明,将溶瘤病毒M1包裹在脂质体中可能会降低固有的病毒免疫原性,从而改善抗癌治疗。通过共聚焦显微镜,使用标记为FITC的M1和标记为RhB的脂质体壳,对细胞摄取M-LPO的分析进行了分析。结果表明,M1可能在M-LPO内化之前或之后从脂质体中释放出来。两者合计,我们的结果表明,将溶瘤病毒M1包裹在脂质体中可能会降低固有的病毒免疫原性,从而改善抗癌治疗。
更新日期:2019-01-03
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