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

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.

Cite this article

Heise, C., Hermiston, T., Johnson, L. et al. An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy. Nat Med 6, 1134–1139 (2000). https://doi.org/10.1038/80474

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