Loss of p14ARF in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015)
- 1 October 2000
- journal article
- research article
- Published by Springer Nature in Nature Medicine
- Vol. 6 (10) , 1128-1133
- https://doi.org/10.1038/80466
Abstract
The adenovirus mutant dl1520 (ONYX-015) does not express the E1B-55K protein that binds and inactivates p53. This virus replicates in tumor cells with mutant p53, but not in normal cells with functional p53. Although intra-tumoral injection of dl1520 shows promising responses in patients with solid tumors, previous in vitro studies have not established a close correlation between p53 status and dl1520 replication. Here we identify loss of p14ARF as a mechanism that allows dl1520 replication in tumor cells retaining wild-type p53. We demonstrate that the re-introduction of p14ARF into tumor cells with wild-type p53 suppresses replication of dl1520 in a p53-dependent manner. Our study supports the therapeutic use of dl1520 in tumors with lesions within the p53 pathway other than mutation of p53.Keywords
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