Tumor-specific gene delivery using recombinant vaccinia virus in a rabbit model of liver metastases
Tumor-specific gene delivery using recombinant vaccinia virus in a rabbit model of liver metastases
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DOI：
10.1093/jnci/91.20.1744
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发表时间：
1999-10-20
期刊：
影响因子：
--
通讯作者：
Bartlett, DL
中科院分区：
文献类型：
--
作者：
Gnant, MFX;Noll, LA;Bartlett, DL
背景：癌症基因治疗的几种方法在啮齿动物模型中取得了可喜的结果。由于缺乏大型动物中的肿瘤模型，这些结果向临床领域的转化被延迟。我们研究了转基因的模式（即，外源或引入的基因）表达和使用胸苷激酶阴性牛痘病毒在播散性肝转移的兔模型中进行系统性基因递送后的病毒载体消除。研究方法：将VX-2兔肝癌细胞连续移植于新西兰白色兔大腿肌肉内，并将肿瘤细胞直接注入动物门静脉建立播散性肝转移瘤。将不同剂量的编码萤火虫荧光素酶报告基因的重组胸苷激酶阴性牛痘病毒载体（即，转基因）注射到荷瘤兔中，此后在多个时间点测量肿瘤和其它器官中的转基因活性，还检查了针对牛痘病毒载体的抗体的发展模式。双尾Student配对t检验用于比较转基因活性。结果：在载体注射后第4天，与在其它组织中的表达相比，转基因表达在肿瘤中增加至少16倍（均P
Background: Several approaches to gene therapy for cancer have yielded promising results in rodent models. The translation of these results to the clinical realm has been delayed by the lack of tumor models in large animals We investigated the pattern of transgene (i.e., foreign or introduced gene) expression and virus vector elimination after systemic gene delivery using a thymidine kinase-negative vaccinia virus in a rabbit model of disseminated liver metastases. Methods: VX-2 rabbit carcinoma cells were maintained by serial transplantation in the thigh muscles of New Zealand White rabbits, and disseminated liver metastases were established by direct injection of tumor cells into the portal vein of the animals. Different doses of a recombinant thymidine kinase-negative vaccinia virus vector encoding the firefly luciferase reporter gene (i.e., transgene) were injected into tumor-bearing rabbits, Transgene activity in tumors and other organs was measured at multiple time points thereafter, The pattern of development of antibodies against the vaccinia virus vector was also examined. Two-tailed Student's paired t test was used for comparisons of transgene activity, Results: Transgene expression was increased in tumors by at least 16-fold in comparison with expression in other tissues by day 4 after vector injection (all P