title: In vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Rogulski
authors.forename: S O
authors.initials: SO
authors.lastname: Freytag
authors.forename: K
authors.initials: K
authors.lastname: Zhang
authors.forename: J D
authors.initials: JD
authors.lastname: Gilbert
authors.forename: D L
authors.initials: DL
authors.lastname: Paielli
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: C C
authors.initials: CC
authors.lastname: Heise
authors.forename: D H
authors.initials: DH
authors.lastname: Kirn
mesh_terms: D000256:Adenoviridae; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D020360:Neoadjuvant Therapy; D009369:Neoplasms / Q000235:genetics* / Q000532:radiotherapy / Q000628:therapy*; D014407:Tumor Cells, Cultured