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

• Published in: Nature medicine Vol. 6; no. 10; pp. 1134 - 1139
• Main Authors: Kirn, David, Heise, Carla, Hermiston, Terry, Johnson, Leisa, Brooks, Gabriel, Sampson-Johannes, Adam, Williams, Angelica, Hawkins, Lyndah
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.10.2000
• Subjects: Adenoviridae - genetics; adenovirus; Adenovirus E1A Proteins - genetics; Adenoviruses; AE1A protein; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Cancer; Care and treatment; Drug Screening Assays, Antitumor; Female; Genetic aspects; Genetic Vectors - administration & dosage; Genetic Vectors - pharmacology; Health aspects; Humans; Injections, Intralesional; Injections, Intravenous; Intravenous administration; Mice; Mice, Nude; Mutants; Neoplasm Metastasis - drug therapy; Neoplasms - drug therapy; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays; United States
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/80474

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.