Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector
Antitumor activity and prolonged expression from a TRAIL-expressing adenoviral vector
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DOI：
10.1038/sj.neo.7900245
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发表时间：
2002-07-01
期刊：
影响因子：
4.8
通讯作者：
Fine, HA
中科院分区：
文献类型：
--
作者：
Lee, JW;Hampl, M;Fine, HA
肿瘤坏死因子相关凋亡诱导配体（TRAIL）在多种转化细胞系中诱导凋亡，但通常不影响大多数正常细胞。通过表达人TRAIL cDNA的腺病毒载体（Ad.TRAIL-GFP）的转导导致直接的肿瘤细胞杀伤以及通过转导的正常细胞呈递TRAIL的有效的旁观者效应。施用Ad.TRAIL-GFP显著延长了携带脑内胶质母细胞瘤或乳腺癌诱导的腹膜癌病的小鼠的存活。此外，TRAIL诱导正常组织中延长的转基因表达，推测是由于载体转导细胞的免疫介导的破坏减少。综上所述，这些数据表明，载体介导的转导的TRAIL可能是一种有效的癌症基因治疗策略。
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of transformed cell lines, but generally spares most normal cells. Transduction by an adenoviral vector expressing human TRAIL cDNA (Ad.TRAIL-GFP) resulted in both direct tumor cell killing as well as a potent bystander effect through presentation of TRAIL by transduced normal cells. Administration of Ad.TRAIL-GFP significantly prolonged survival of mice harboring either intracerebral glioblastomas or breast carcinoma-induced peritoneal carcinomatosis. Additionally, TRAIL induced prolonged transgene expression in normal tissue, presumably as a result of diminished immune-mediated destruction of vector - transduced cells. Taken together, these data suggest that vector-mediated transduction of TRAIL may represent an effective strategy for cancer gene therapy.