Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth
Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth
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DOI：
10.1038/nm0497-437
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发表时间：
1997-04-01
期刊：
影响因子：
82.9
通讯作者：
Fine, HA
中科院分区：
文献类型：
--
作者：
Tanaka, T;Manome, Y;Fine, HA
治疗性蛋白质如血管生成抑制剂的慢性全身递送提出了许多困难的药理学挑战。为了克服这些问题的一个这样的蛋白质，我们构建了逆转录病毒和腺病毒载体，表达一种新的，分泌形式的抗血管生成蛋白，血小板因子4（sPF 4）。载体介导的sPF 4转导在体外选择性地抑制内皮细胞增殖，并导致在体内缓慢生长的少血管肿瘤。此外，肿瘤相关的血管生成被抑制，动物的生存期延长，建立脑内胶质瘤转导的sPF 4表达腺病毒载体。这些数据支持的概念，有针对性的抗血管生成，使用病毒介导的基因转移，提供抗血管生成治疗的一个有前途的战略。
Chronic systemic delivery of therapeutic proteins, such as inhibitors of angiogenesis, present a number of difficult pharmacological challenges. To overcome these problems for one such protein, we constructed retroviral and adenoviral vectors that express a novel, secretable form of the antiangiogenic protein, platelet factor 4 (sPF4). Vector-mediated sPF4 transduction selectively inhibits endothelial cell proliferation in vitro, and results in hypovascular tumors that grow slowly in vivo. Additionally, tumor-associated angiogenesis is inhibited and animal survival is prolonged, following transduction of established intracerebral gliomas by an sPF4-expressing adenoviral vector. These data support the concept that targeted antiangiogenesis, using virally mediated gene transfer, represents a promising strategy for delivering antiangiogenic therapy.