Double-faceted mechanism of parvoviral oncosuppression
Double-faceted mechanism of parvoviral oncosuppression
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DOI：
10.1016/j.coviro.2015.03.008
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发表时间：
2015-08-01
影响因子：
5.9
通讯作者：
Rommelaere, Jean
中科院分区：
文献类型：
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作者：
Geletneky, Karsten;Nueesch, Juerg P. F.;Rommelaere, Jean
H-1细小病毒（H-1 PV）的抑瘤作用有两个组成部分：肿瘤毒性和免疫刺激。虽然许多人类肿瘤细胞，包括传统的耐药细胞，可以被H-1 PV杀死，但有些不能支持子代病毒的产生，这是肿瘤组织中感染传播所必需的。这种限制可以通过强制选择能够在人类肿瘤细胞中增强增殖和扩散的H-1 PV变体来克服。在进一步开发用于癌症治疗的H-1 PV的背景下，在保留复制和溶瘤的条件下用免疫刺激性CpG基序武装它增强了它作为抗癌疫苗佐剂的作用。在神经胶质瘤患者中进行的第一项H-1 PV治疗的临床研究已经产生了肿瘤内病毒致癌蛋白NS 1合成和免疫细胞浸润的证据。
The H-1 parvovirus (H-1PV) exerts oncosuppressive action that has two components: oncotoxicty and imnnunostimulation. While many human tumor cells, including conventional drug-resistant ones, can be killed by H-1PV, some fail to support progeny virus production, necessary for infection propagation in neoplastic tissues. This limitation can be overcome through forced selection of H-1PV variants capable of enhanced multiplication and spreading in human tumor cells. In the context of further developing H-1PV for use in cancer therapy, arming it with immunostimulatory CpG motifs under conditions preserving replication and oncolysis enhances its action as an anticancer vaccine adjuvant. A first clinical study of H-1PV treatment in glioma patients has yielded evidence of intratumoral synthesis of the viral oncotoxic protein NS1 and immune cell infiltration.