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- Title
Loss of p14<sup>ARF</sup> in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015).
- Authors
Ries, Stefan J.; Brandts, Christian H.; Chung, Alicia S.; Biederer, Carola H.; Hann, Byron C.; Lipner, Ettie M.; McCormick, Frank; Michael Korn, W.
- 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 p14[sup ARF] as a mechanism that allows dl1520 replication in tumor cells retaining wild-type p53. We demonstrate that the re-introduction of p14[sup ARF] 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.
- Publication
Nature Medicine, 2000, Vol 6, Issue 10, p1128
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/80466