Heat 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...

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Bibliographic Details
Published in:Cancer cell 2005-07, Vol.8 (1), p.61-74
Main Authors: O’Shea, Clodagh C., Soria, Conrado, Bagus, Bridget, McCormick, Frank
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - metabolism
Adenoviridae - physiology
Adenovirus
Adenovirus E1B Proteins - genetics
Adenovirus E1B Proteins - metabolism
Antineoplastic Agents - therapeutic use
Cells, Cultured
Cytopathogenic Effect, Viral - genetics
Drug Resistance, Neoplasm
Hot Temperature - therapeutic use
Humans
Neoplasms - metabolism
Neoplasms - therapy
Neoplasms - virology
Phenotype
RNA Transport
RNA, Viral - metabolism
Shock - therapy
Viral Nonstructural Proteins - metabolism
Viral Vaccines
Virus Replication - genetics
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Summary: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 100K mRNA export is necessary for host protein shutoff. However, heat shock rescues late viral RNA export and renders refractory tumor cells permissive to ONYX-015. These data indicate that heat shock and late adenoviral RNAs may converge upon a common mechanism for their export. Moreover, these data suggest that the concomitant induction of a heat shock response could significantly improve ONYX-015 cancer therapy.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2005.06.009