Fusogenic activity of vesicular stomatitis virus glycoprotein plasmid in tumors as an enhancer of IL-12 gene therapy
Fusogenic activity of vesicular stomatitis virus glycoprotein plasmid in tumors as an enhancer of IL-12 gene therapy
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DOI：
10.1038/sj.cgt.7700270
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发表时间：
2001-01-01
影响因子：
6.4
通讯作者：
Pericle, F
中科院分区：
文献类型：
--
作者：
Eslahi, NK;Muller, S;Pericle, F
我们的特点是融合活性的质粒表达系统编码水泡性口炎病毒G蛋白（VSVG）在体外和体内。体外转染VSVC质粒的小鼠结肠癌和肾癌细胞（分别为MC 38和Renca）在pH5.5的培养基中培养时融合并形成多核体。使用在聚乙烯吡咯烷酮（PVP）递送系统中配制的编码VSVG和细菌绿色荧光蛋白（GFP）的质粒表达系统，在MC 38和Renca肿瘤中显示GFP在VSVG诱导的合胞体中的体内扩散。此外，荷瘤小鼠在体内转染VSVG质粒后显示出肿瘤生长抑制，最佳剂量为48 μ g。我们以前已经表明，直接注射与PVP复合的白细胞介素-12（IL-12）质粒到肿瘤中诱导强烈的免疫应答。在目前的研究中，我们评估了VSVG通过增强肿瘤块内细胞因子基因递送引起抗肿瘤反应的能力。与单独的IL-12质粒相比，肿瘤内用VSVG/PVP和IL-12/PVP（分别为48 μ g和24 μ g）治疗的荷瘤小鼠显示肿瘤排斥增加（分别为75%对50%）。这些数据表明，VSVG基因治疗可以与其他治疗基因组合使用，以通过增强感兴趣的基因的表达来诱导体内抗肿瘤反应。
We have characterized the fusogenic activity of a plasmid expression system encoding vesicular stomatitis virus G protein (VSVG) in vitro and in vivo. Over 70% of murine colon and renal carcinoma cells (MC38 and Renca, respectively) transfected with VSVC plasmid in vitro fused and formed polykaryons upon incubation with pH 5.5 media. Using a plasmid expression system encoding VSVG and bacterial green fluorescent protein (GFP) formulated in a polyvinyl pyrrolidone (PVP) delivery system, diffusion of GFP throughout the VSVG-induced syncytia was shown in vivo in MC38 and Renca tumors. Moreover, tumor-bearing mice showed tumor growth inhibition following in vivo transfection with VSVG plasmid at an optimal dose of 48 mug. We have previously shown that direct injection of interleukin-12 (IL-12) plasmid complexed with PVP into tumors induces a strong immune response. In the current study, we assessed the ability of VSVG to elicit an antitumor response by enhancing cytokine gene delivery within the tumor mass. Tumor-bearing mice treated intratumorally with both VSVG/PVP and IL-12/PVP (48 and 24 mug, respectively) showed increase in tumor rejection when compared to IL-12 plasmid alone (75% vs. 50%, respectively). These data suggest that VSVG gene therapy can be used in combination with other therapeutic genes to induce an antitumor response in vivo by enhancing the expression of the gene of interest.