Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity
نویسندگان
چکیده
منابع مشابه
Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity.
ONYX-015 is an adenovirus that lacks the E1B-55K gene product for p53 degradation. Thus, ONYX-015 was conceived as an oncolytic virus that would selectively replicate in p53-defective tumor cells. Here we show that loss of E1B-55K leads to the induction, but not the activation, of p53 in ONYX-015-infected primary cells. We use a novel adenovirus mutant, ONYX-053, to demonstrate that loss of E1B...
متن کاملHeat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy.
ONYX-015 is an E1B-55K-deleted adenovirus that has promising clinical activity as a cancer therapy. However, many tumor cells fail to support ONYX-015 oncolytic replication. E1B-55K functions include p53 degradation, RNA export, and host protein shutoff. Here, we show that resistant tumor cell lines fail to provide the RNA export functions of E1B-55K necessary for ONYX-015 replication; viral 10...
متن کاملReplication of ONYX-015, a potential anticancer adenovirus, is independent of p53 status in tumor cells.
The 55-kDa E1B protein of adenovirus, which binds to and inactivates the tumor suppressor protein p53, is not expressed in the adenoviral mutant termed ONYX-015 (i.e., dl1520). It was reported that the mutant virus due to a deletion in E1B is able to replicate only in cells deficient for wild-type p53. Accordingly, dl1520 is currently being evaluated as a potential tool in the therapy of p53 de...
متن کاملReplication of an E1B 55-kilodalton protein-deficient adenovirus (ONYX-015) is restored by gain-of-function rather than loss-of-function p53 mutants.
ONYX-015 (dl1520) is an E1B 55-kilodalton protein-deficient replicating adenovirus that is currently in clinical trials as an antitumor agent. On the basis of the observation that the E1B 55kD gene product is able to bind to and inactivate p53, ONYX-015's mechanism of action is proposed to involve selective replication in and killing of p53-deficient cells. While its efficacy as a therapeutic a...
متن کاملIn vivo antitumor activity of ONYX-015 is influenced by p53 status and is augmented by radiotherapy.
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. Us...
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ژورنال
عنوان ژورنال: Cancer Cell
سال: 2004
ISSN: 1535-6108
DOI: 10.1016/j.ccr.2004.11.012