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  • Title: Loss of p14ARF in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015).
    Author: Ries SJ, Brandts CH, Chung AS, Biederer CH, Hann BC, Lipner EM, McCormick F, Korn WM.
    Journal: Nat Med; 2000 Oct; 6(10):1128-33. PubMed ID: 11017144.
    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.
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