The macrophage - a novel system to deliver gene therapy to pathological hypoxia
The macrophage - a novel system to deliver gene therapy to pathological hypoxia
复制标题
DOI：
10.1038/sj.gt.3301058
复制
发表时间：
2000-02-01
期刊：
影响因子：
5.1
通讯作者：
Naylor, S
中科院分区：
文献类型：
--
作者：
Griffiths, L;Binley, K;Naylor, S
活化的巨噬细胞在癌症治疗中的应用在很大程度上是无效的。通过“武装”这些细胞表达治疗基因的能力，我们证明了这种方法的功效的显着进步。我们使用低氧调节的腺病毒载体，以报告基因或治疗基因编码的人细胞色素P4502B6（CYP2B6）的人巨噬细胞。转导的巨噬细胞浸润到肿瘤球体中导致基因表达的诱导。我们证明了只有在环磷酰胺存在的情况下，通过P4502B6的激活才能杀死显著的肿瘤细胞，并表明这可以通过缺氧调节的基因表达进一步靶向肿瘤。
The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression.