An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy
An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy
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DOI：
10.1038/80474
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发表时间：
2000-10-01
期刊：
影响因子：
82.9
通讯作者：
Kirn, D
中科院分区：
文献类型：
--
作者：
Heise, C;Hermiston, T;Kirn, D
复制选择性溶瘤病毒是一种快速发展的新型癌症治疗平台。基因缺失的病毒已被设计为具有肿瘤选择性，但这些基因缺失也降低了病毒的抗癌效力。我们已经确定了一种E1A突变腺病毒dl922-947，它在细胞周期检查点异常的癌细胞中复制并溶解大量癌细胞。该突变体在非增殖正常细胞中表现出s期诱导和复制减少，相对于其他基因缺失腺病毒具有更高的体内效力。在某些癌症中，其效力甚至优于野生型腺病毒。静脉给药降低了乳腺肿瘤异种移植模型的转移发生率。Dl922-947有望成为一种有效的、具有复制选择性的病毒，用于局部和全身癌症治疗。
Replication-selective oncolytic viruses constitute a rapidly evolving and new treatment platform for cancer. Gene-deleted viruses have been engineered for tumor selectivity, but these gene deletions also reduce the anti-cancer potency of the viruses. We have identified an E1A mutant adenovirus, dl922-947, that replicates in and lyses a broad range of cancer cells with abnormalities in cell-cycle checkpoints. This mutant demonstrated reduced S-phase induction and replication in non-proliferating normal cells, and superior in vivo potency relative to other gene-deleted adenoviruses. In some cancers, its potency was superior to even wild-type adenovirus. Intravenous administration reduced the incidence of metastases in a breast tumor xenograft model. dl922-947 holds promise as a potent, replication-selective virus for the local and systemic treatment of cancer.