Loss of p14ARF in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015)
Author: ["Stefan J. Ries","Christian H. Brandts","Alicia S. Chung","Carola H. Biederer","Byron C. Hann","Ettie M. Lipner","Frank McCormick","W. Michael Korn"]
Publication: Nature Medicine
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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.
Cite this article
Ries, S., Brandts, C., Chung, A. et al. Loss of p14ARF in tumor cells facilitates replication of the adenovirus mutant dl1520 (ONYX-015). Nat Med 6, 1128–1133 (2000). https://doi.org/10.1038/80466
