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Adenovirus-retrovirus Hybrid Vectors Achieve Highly Enhanced Tumor Transduction and Antitumor Efficacy in Vivo

Overview
Journal Mol Ther
Publisher Cell Press
Date 2010 Sep 3
PMID 20808291
Citations 6
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Abstract

Murine leukemia virus (MLV)-based replication-competent retrovirus (RCR) vectors have been shown to mediate efficient, selective, and persistent tumor transduction, thereby achieving significant therapeutic benefit in a wide variety of cancer models. To further augment the efficiency of this strategy, we have developed a delivery method employing a gutted adenovirus encoding an RCR vector (AdRCR); thus, tumor cells transduced with the adenoviral vector transiently become RCR vector producer cells in situ. As expected, high-titer AdRCR achieved significantly higher initial transduction levels in human cancer cells both in vitro and in vivo, as compared to the original RCR vector itself. Notably, even at equivalent initial transduction levels, more secondary RCR progeny were produced from AdRCR-transduced cells as compared to RCR-transduced cells, resulting in further acceleration of subsequent RCR replication kinetics. In pre-established tumor models in vivo, prodrug activator gene therapy with high-titer AdRCR could achieve enhanced efficacy compared to RCR alone, in a dose-dependent manner. Thus, AdRCR hybrid vectors offer the advantages of high production titers characteristic of adenovirus and secondary production of RCR in situ, which not only accelerates subsequent vector spread and progressive tumor transduction, but can also significantly enhance the therapeutic efficacy of RCR-mediated prodrug activator gene therapy.

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References
1.
Liu T, Kirn D . Gene therapy progress and prospects cancer: oncolytic viruses. Gene Ther. 2008; 15(12):877-84. DOI: 10.1038/gt.2008.72. View

2.
Wang W, Tai C, Kershaw A, Solly S, Klatzmann D, Kasahara N . Use of replication-competent retroviral vectors in an immunocompetent intracranial glioma model. Neurosurg Focus. 2006; 20(4):E25. PMC: 8295718. DOI: 10.3171/foc.2006.20.4.1. View

3.
Palmer D, Ng P . Improved system for helper-dependent adenoviral vector production. Mol Ther. 2003; 8(5):846-52. DOI: 10.1016/j.ymthe.2003.08.014. View

4.
Volpers C, Kochanek S . Adenoviral vectors for gene transfer and therapy. J Gene Med. 2004; 6 Suppl 1:S164-71. DOI: 10.1002/jgm.496. View

5.
Sena-Esteves M, Saeki Y, Camp S, Chiocca E, Breakefield X . Single-step conversion of cells to retrovirus vector producers with herpes simplex virus-Epstein-Barr virus hybrid amplicons. J Virol. 1999; 73(12):10426-39. PMC: 113098. DOI: 10.1128/JVI.73.12.10426-10439.1999. View