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

Replication-selective oncolytic viruses constitute a rapidly evolving and n ew treatment platform for cancer. Gene-deleted viruses have been engineered for tumor selectivity, but these gene deletions also reduce the anti-cance r potency of the viruses. We have identified an E1A mutant adenovirus, dl92 2-947, that replicates in and lyses a broad range of cancer cells with abno rmalities in cell-cycle checkpoints. This mutant demonstrated reduced S-pha se induction and replication in non-proliferating normal cells, and superio r in vivo potency relative to other gene-deleted adenoviruses. In some canc ers, its potency was superior to even wild-type adenovirus. Intravenous adm inistration reduced the incidence of metastases in a breast tumor xenograft model. dl922-947 holds promise as a potent, replication-selective virus fo r the local and systemic treatment of cancer.