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. 2000 Oct;6(10):1134-9.
doi: 10.1038/80474.

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

C Heise  1 , T Hermiston, L Johnson, G Brooks, A Sampson-Johannes, A Williams, L Hawkins, D Kirn
Affiliations

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

C Heise et al. Nat Med. 2000 Oct.

Erratum in

  • Nat Med 2000 Dec;6(12):1412

Abstract

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.

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