Tegerstedt Karin, Franzén Andrea Vlastos, Andreasson Kalle, Joneberg Jeanna, Heidari Shirin, Ramqvist Torbjörn, Dalianis Tina
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8: 01, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Anticancer Res. 2005 Jul-Aug;25(4):2601-8.
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.
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。