Cytokine-induced killer cell delivery enhances the antitumor activity of oncolytic reovirus.

Cytokine-induced killer cell delivery enhances the antitumor activity of oncolytic reovirus.
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细胞因子诱导的杀伤细胞递送增强溶瘤呼肠孤病毒的抗肿瘤活性

DOI:
10.1371/journal.pone.0184816
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
He Z
He Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao X;Ouyang W;Chester C;Long S;Wang N;He Z

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溶瘤病毒(OV)最近已成为一种有前途的治疗模式,在癌症治疗。OV选择性地感染和杀死肿瘤细胞,而不伤害未转化的细胞。直接的细胞毒性作用与触发免疫反应的能力相结合,使OV成为新兴的癌症免疫治疗领域中有吸引力的组合伙伴。一种主要的OV治疗候选物是双链RNA病毒呼肠孤病毒。为了改善呼肠孤病毒的溶瘤活性并允许尽管中和抗体普遍存在但仍全身施用,探索了奎宁诱导的杀伤(CIK)细胞作为用于呼肠孤病毒递送的细胞载体。在这项研究中,CIK细胞成功地与呼肠孤病毒离体负载,和病毒复制在CIK细胞中是有限的。共聚焦显微镜和流式细胞术证实CIK细胞表面保留有呼肠孤病毒。此外,CIK细胞在中和抗体存在下可促进呼肠孤病毒感染肿瘤细胞;同时,CIK细胞负载呼肠孤病毒后的细胞毒性增加。这些发现支持进一步研究呼肠孤病毒和CIK组合用于抗肿瘤治疗。
Oncolytic viruses (OV) have recently emerged as a promising therapeutic modality in cancer treatment. OV selectively infect and kill tumor cells, while sparing untransformed cells. The direct cytotoxic effects combined with the capacity to trigger an immune response make OV an appealing combination partner in the burgeoning field of cancer immunotherapy. One of the leading OV therapeutic candidates is the double-stranded RNA virus reovirus. In order to improve the oncolytic activity of reovirus and allow for systemic administration despite the prevalence of neutralizing antibodies, cytokine-induced killer (CIK) cells were explored as cell carriers for reovirus delivery. In this study, CIK cells were successfully loaded with reovirus ex vivo, and viral replication was limited in CIK cells. Confocal microscopy and flow cytometry demonstrated that CIK cells retained reovirus on the surface. Moreover, CIK cells could promote reovirus infection of tumor cells in the presence of neutralizing antibodies; meanwhile, cytotoxicity of CIK cells was increased after loading with reovirus. These findings support further investigation of reovirus and CIK combination for antitumor therapy.
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