纤维替代条件复制腺病毒用于人类肾癌细胞的溶瘤治疗。
Fiber-substituted conditionally replicating adenovirus for oncolysis of human renal carcinoma cells.
机构信息
Laboratory of Cell and Gene Therapy, Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
出版信息
Anticancer Res. 2012 Jul;32(7):2985-9.
BACKGROUND
Adenovirus vectors have lately been highlighted in gene therapies. We investigated the oncolytic effects of a chimeric adenovirus type 5 (Ad5) with replacement of Ad5 fiber knob with adenovirus type 35 (Ad35) fiber knob (Ad5F35) on human renal cell carcinoma (RCC).
MATERIALS AND METHODS
The conditionally replicating Ad5F35 vector was constructed and infected into RCC cell lines 786-O, ACHN, and RCC4-VHL. For these cells, reverse transcription-polymerase chain reaction and western blotting were carried out and the cell viability was assayed.
RESULTS
In all RCC cell lines, it was found that CD46, a cell surface target of Ad35, was well-expressed, while coxsackie and adenovirus receptor (CAR), a cell surface target of Ad5, was considerably less expressed. The Ad5F35 vector induced oncolysis of RCC cells, with significantly higher efficacy as compared with that for the Ad5 vector.
CONCLUSION
Ad5F35 vector could be a candidate for promising gene therapy of human RCC.
背景
腺病毒载体最近在基因治疗中受到了关注。我们研究了用腺病毒 35 型（Ad35）纤维结替换腺病毒 5 型（Ad5）纤维结的嵌合腺病毒 5 型（Ad5F35）对人肾细胞癌（RCC）的溶瘤作用。
材料与方法
构建了条件复制的 Ad5F35 载体，并感染 RCC 细胞系 786-O、ACHN 和 RCC4-VHL。对这些细胞进行逆转录-聚合酶链反应和 Western blot 分析，并检测细胞活力。
结果
在所有 RCC 细胞系中，发现 Ad35 的细胞表面靶标 CD46 表达良好，而 Ad5 的细胞表面靶标柯萨奇病毒和腺病毒受体（CAR）表达显著减少。Ad5F35 载体诱导 RCC 细胞溶瘤，其疗效明显高于 Ad5 载体。
结论
Ad5F35 载体可能是治疗人 RCC 的有前途的基因治疗候选物。
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