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.

• Authors: C Heise, T Hermiston, L Johnson, G Brooks, A Sampson-Johannes, A Williams, L Hawkins, D Kirn
• Journal: Nature medicine (Nat Med) Vol. 6 Issue 10 Pg. 1134-9 (Oct 2000) ISSN: 1078-8956 [Print] United States
• PMID: 11017145 (Publication Type: Evaluation Study, Journal Article)

Chemical References

• Adenovirus E1A Proteins
• Antineoplastic Agents

Topics

• Adenoviridae (genetics)
• Adenovirus E1A Proteins (genetics)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Genetic Vectors (administration & dosage, pharmacology)
• Humans
• Injections, Intralesional
• Injections, Intravenous
• Mice
• Mice, Nude
• Neoplasm Metastasis (drug therapy)
• Neoplasms (drug therapy)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays