An adenovirus E1A mutant that demonstrates potent and selective systemic anti-tumoral efficacy.
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.
Heise
C
C
Chiron Corporation, Emeryville, California, USA.
Hermiston
T
T
Johnson
L
L
Brooks
G
G
Sampson-Johannes
A
A
Williams
A
A
Hawkins
L
L
Kirn
D
D
D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents