An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy

被引:497
作者
Heise, C
Hermiston, T
Johnson, L
Brooks, G
Sampson-Johannes, A
Williams, A
Hawkins, L
Kirn, D [1 ]
机构
[1] Hammersmith Hosp, Imperial Coll Sch Med, Imperial Canc Res Fund, Viral & Genet Therapy Programme, London W12 0HS, England
[2] Onyx Pharmaceut, Richmond, CA USA
[3] Berlex Biosci, Richmond, CA USA
[4] Chiron Corp, Emeryville, CA 94608 USA
关键词
D O I
10.1038/80474
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1134 / 1139
页数:6
相关论文
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