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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Acknowledgements
We thank O. Diri and Y. Dugan for preparation of this manuscript; S. Weber and M. Lemmon for animal studies; M. Propst for cell culture and viral assays; P. Roo for in situ hybridization; F. McCormick for inspiration and discussions; and P. Trown, E. Fearon, A. Balmain, E. Harlow, D. Hanahan, O. Witte and A. Fattaey for discussions.
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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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DOI: https://doi.org/10.1038/80474
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