RT Journal Article
SR Electronic
T1 <em>In Vivo</em> Antitumor Activity of ONYX-015 Is Influenced by <em>p53</em> Status and Is Augmented by Radiotherapy
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 1193
OP 1196
VO 60
IS 5
A1 Rogulski, Kenneth R.
A1 Freytag, Svend O.
A1 Zhang, Kang
A1 Gilbert, Jeff D.
A1 Paielli, Dell L.
A1 Kim, Jae Ho
A1 Heise, Carla C.
A1 Kirn, David H.
YR 2000
UL http://cancerres.aacrjournals.org/content/60/5/1193.abstract
AB 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.