In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy.

Abstract

The E1B-deleted, replication-competent ONYX-015 (dl1520) adenovirus was originally described as being able to selectively kill p53-deficient cells due to a requirement of p53 inactivation for efficient viral replication. This hypothesis has become controversial because subsequent in vitro studies have demonstrated that the host range specificity of ONYX-015 is independent of p53 gene status. Using a pair of isogenic cell lines that differ only in their p53 status, we demonstrate here that although ONYX-015 can replicate in both p53 wild-type and mutant cells in vitro, the virus demonstrates significantly greater antitumor activity against mutant p53 tumors in vivo. Moreover, ONYX-015 viral therapy can be combined with radiation to improve tumor control beyond that of either monotherapy. The results demonstrate that ONYX-015 can discern in vivo between tumors having a different p53 status and that it may be an effective neoadjuvant to radiation therapy.

• Authors: K R Rogulski, S O Freytag, K Zhang, J D Gilbert, D L Paielli, J H Kim, C C Heise, D H Kirn
• Journal: Cancer research (Cancer Res) Vol. 60 Issue 5 Pg. 1193-6 (Mar 01 2000) ISSN: 0008-5472 [Print] United States
• PMID: 10728673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

• Adenoviridae
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Genes, p53
• Humans
• Mutation
• Neoadjuvant Therapy
• Neoplasms (genetics, radiotherapy, therapy)
• Tumor Cells, Cultured