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鼠多瘤病毒样颗粒(VLPs)作为基因治疗、免疫治疗以及抗病毒感染和癌症疫苗的载体。

Murine polyomavirus virus-like particles (VLPs) as vectors for gene and immune therapy and vaccines against viral infections and cancer.

作者信息

Tegerstedt Karin, Franzén Andrea Vlastos, Andreasson Kalle, Joneberg Jeanna, Heidari Shirin, Ramqvist Torbjörn, Dalianis Tina

机构信息

Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8: 01, Karolinska University Hospital, 171 76 Stockholm, Sweden.

出版信息

Anticancer Res. 2005 Jul-Aug;25(4):2601-8.

Abstract

This review describes the use of murine polyomavirus "virus-like" particles (MPyV-VLPs), free from viral genes, as vectors for gene and immune therapy and as vaccines. For large-scale MPyV-VLP manufacture, VP1 is produced in a baculovirus insect cell system, E. coli or in yeast. MPyV-VLPs bind eukaryotic DNA and introduce this DNA into various cell types in vitro and in vivo. In normal and T-cell-deficient mice, this results in the production of anti-MPyV-VLP (and MPyV) antibodies. Furthermore, repeated MPyV-VLP vaccination has been shown to prevent primary MPyV infection in normal and T-cell-deficient mice, and the outgrowth of some MPyV-induced tumours in normal mice. Moreover, when inoculated with gene constructs encoding for HIV p24, MPyV-VLPs augment the antibody response to p24. In addition, MPyV-VLPs, containing fusion proteins between the VP2 or VP3 capsid protein and selected antigens, can be used as vaccines. Notably, one vaccination with MPyV-VLPs, containing a fusion protein between VP2 and the extracellular and transmembrane parts of the HER-2/neu oncogene, immunizes against outgrowth of a HER-2/neu-expressing tumour in Balb/c mice and also against the development of mammary carcinomas in BALB-neuT transgenic mice. Finally, a second polyoma VLP-vector based on murine pneumotropic virus (MPtV-VLP), which does not cross-react serologically with MPyV-VLP (and MPyV), has been developed and can be used to conduct prime boost gene and immune therapy and vaccination. In summary, MPyV-VLPs are useful vectors for gene therapy, immune therapy and as vaccines and, in combination with MPyV-VLPs, MPtV-VLPs are potentially useful as prime-boost vectors.

摘要

本综述描述了不含病毒基因的鼠多瘤病毒“病毒样”颗粒(MPyV-VLPs)作为基因治疗、免疫治疗载体及疫苗的应用。为大规模生产MPyV-VLPs,VP1可在杆状病毒昆虫细胞系统、大肠杆菌或酵母中产生。MPyV-VLPs能结合真核生物DNA,并将该DNA导入体外和体内的多种细胞类型。在正常小鼠和T细胞缺陷小鼠中,这会导致抗MPyV-VLPs(及MPyV)抗体的产生。此外,重复接种MPyV-VLPs已被证明可预防正常小鼠和T细胞缺陷小鼠的原发性MPyV感染,以及正常小鼠中某些MPyV诱导肿瘤的生长。而且,当接种编码HIV p24的基因构建体时,MPyV-VLPs可增强对p24的抗体反应。此外,含有VP2或VP3衣壳蛋白与选定抗原之间融合蛋白的MPyV-VLPs可作为疫苗使用。值得注意的是,接种一次含有VP2与HER-2/neu癌基因细胞外和跨膜部分之间融合蛋白的MPyV-VLPs,可使Balb/c小鼠对表达HER-2/neu的肿瘤生长产生免疫,也可预防BALB-neuT转基因小鼠发生乳腺癌。最后,已开发出一种基于嗜肺鼠病毒的第二种多瘤病毒VLP载体(MPtV-VLP),它与MPyV-VLPs(及MPyV)在血清学上无交叉反应,可用于进行初免-加强基因治疗、免疫治疗及疫苗接种。总之,MPyV-VLPs是基因治疗、免疫治疗及疫苗的有用载体,与MPyV-VLPs联合使用时,MPtV-VLPs作为初免-加强载体可能具有实用价值。

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