Enhanced efficiency of prodrug activation therapy by tumor-selective replicating retrovirus vectors armed with the Escherichia coli purine nucleoside phosphorylase gene
Cancer Gene Therapy, ISSN: 0929-1903, Vol: 17, Issue: 9, Page: 614-623
2010
- 35Citations
- 20Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations35
- Citation Indexes35
- 35
- CrossRef26
- Captures20
- Readers20
- 20
Article Description
Gene transfer of the Escherichia coli purine nucleoside phosphorylase (PNP) results in potent cytotoxicity after administration of the prodrug fludarabine phosphate (F-araAMP). Here, we have tested whether application of this strategy in the context of replication-competent retrovirus (RCR) vectors, which can achieve highly efficient tumor-restricted transduction as well as persistent expression of transgenes, would result in effective tumor inhibition, or, alternatively, would adversely affect viral replication. We found that RCR vectors could achieve high levels of PNP expression concomitant with the efficiency of their replicative spread, with significant cell killing activity in vitro and potent therapeutic effects in vivo. In U-87 xenograft models, replicative spread of the vector resulted in progressive transmission of the PNP transgene, as evidenced by increasing PNP enzyme activity with time after vector inoculation. On F-araAMP administration, high efficiency gene transfer of PNP by the RCR vector resulted in significant suppression of tumor growth and extended survival time. As the RCR mediates stable integration of the PNP gene and continuous expression, an additional round of F-araAMP administration resulted in further survival benefit. RCR-mediated PNP suicide gene therapy thus represents a highly efficient form of intracellular chemotherapy, and may achieve effective antitumor activity with less systemic toxicity. © 2010 Nature America, Inc. All rights reserved.
Bibliographic Details
Springer Science and Business Media LLC
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