Taming the Trojan horse: optimizing dynamic carrier cell/oncolytic virus systems for cancer biotherapy

Power, Anthony; Bell, John C.

doi:10.1038/gt.2008.40

Cited by 64 publications

(51 citation statements)

References 27 publications

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“…Previous studies have explored the use of virusinfected cells as carriers to protect and transport the virus to sites of tumor growth (48)(49)(50)(51) or synthetic polymers to coat and protect the virus from antibody neutralization (39,52) or have employed G protein evolution strategies to generate neutralization-resistant variants of VSV G (53). However, each of these approaches has its limitations.…”

Section: Discussionmentioning

confidence: 99%

Vesiculovirus Neutralization by Natural IgM and Complement

Tesfay

Ammayappan

Federspiel

et al. 2014

J Virol

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Because of its very low human seroprevalence, vesicular stomatitis virus (VSV) has promise as a systemic oncolytic agent for human cancer therapy. However, as demonstrated in this report, the VSV infectious titer drops by 4 log units during the first hour of exposure to nonimmune human serum. This neutralization occurs relatively slowly and is mediated by the concerted actions of natural IgM and complement. Maraba virus, whose G protein is about 80% homologous to that of VSV, is relatively resistant to the neutralizing activity of nonimmune human serum. We therefore constructed and rescued a recombinant VSV whose G gene was replaced by the corresponding gene from Maraba virus. Comparison of the parental VSV and VSV with Maraba G substituted revealed nearly identical host range properties and replication kinetics on a panel of tumor cell lines. Moreover, in contrast to the parental VSV, the VSV with Maraba G substituted was resistant to nonimmune human serum. Overall, our data suggest that VSV with Maraba G substituted should be further investigated as a candidate for human systemic oncolytic virotherapy applications. IMPORTANCEOncolytic virotherapy is a promising approach for the treatment of disseminated cancers, but antibody neutralization of circulating oncolytic virus particles remains a formidable barrier. In this work, we developed a pseudotyped vesicular stomatitis virus (VSV) with a glycoprotein of Maraba virus, a closely related but serologically distinct member of the family Rhabdoviridae, which demonstrated greatly diminished susceptibility to both nonimmune and VSV-immune serum neutralization. VSV with Maraba G substituted or lentiviral vectors should therefore be further investigated as candidates for human systemic oncolytic virotherapy and gene therapy applications.

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Section: Discussionmentioning

confidence: 99%

Vesiculovirus Neutralization by Natural IgM and Complement

Tesfay

Ammayappan

Federspiel

et al. 2014

J Virol

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“…The conditional replicative viruses are able to replicate and cause cell lysis only in the targeted tumor cells. In addition, the replicated viruses are able to infect neighboring cancer cells and continue this infection cycle until all of the tumor cells are eradicated (78). Virotherapy is the strategy of using a replication-competent virus for cancer therapy.…”

Section: Transcriptionally Regulated Oncolytic Adenovirusesmentioning

confidence: 99%

Adenovirus-mediated cancer gene therapy and virotherapy (Review)

Fukazawa¹

2009

Int J Mol Med

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Abstract. Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells. Recently, novel cancer-and/or tissue-specific promoter systems have been developed to target cancer cells but not normal cells including stem cells. In this review, we describe cancer and/or tissue-specific gene therapy systems for the treatment of cancer. In particular, we will discuss three systems for gene therapy and virotherapy: i) tissue-specific promoter systems, ii) cancer-specific promoter systems, and iii) oncolytic virotherapy. We will also discuss the major challenges of cancer-targeting vector systems and future directions in this area.

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“…Many mechanisms indeed account for the tumoricidal activity of oncolytic viruses (4). Ras transformation promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, virus release through apoptosis, and finally precludes IFN production following reovirus infection, permitting enhanced cell-to-cell virus spread (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%