Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors

Wu, Yuping; Lun, Xueqing; Zhou, Hongyuan; Wang, Limei; Sun, Beichen; Bell, John C.; Barrett, John W.; McFadden, Grant; Biegel, Jaclyn A.; Senger, Donna L.; Forsyth, Peter

doi:10.1158/1078-0432.ccr-07-1330

Cited by 52 publications

(46 citation statements)

References 44 publications

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“…2a,b). In agreement with experimental observations in a variety of tumour models 6,26,27 , our simulations predict that the D51-attenuated virus will eradicate IFN non-responsive tumours, whereas normal populations or IFN-responsive tumours will be largely resistant (Fig. 2c,d).…”

Section: Resultssupporting

confidence: 88%

Model-based rational design of an oncolytic virus with improved therapeutic potential

et al. 2013

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Oncolytic viruses are complex biological agents that interact at multiple levels with both tumour and normal tissues. Antiviral pathways induced by interferon are known to have a critical role in determining tumour cell sensitivity and normal cell resistance to infection with oncolytic viruses. Here we pursue a synthetic biology approach to identify methods that enhance antitumour activity of oncolytic viruses through suppression of interferon signalling. On the basis of the mathematical analysis of multiple strategies, we hypothesize that a positive feedback loop, established by virus-mediated expression of a soluble interferon-binding decoy receptor, increases tumour cytotoxicity without compromising normal cells. Oncolytic rhabdoviruses engineered to express a secreted interferon antagonist have improved oncolytic potential in cellular cancer models, and display improved therapeutic potential in tumour-bearing mice. Our results demonstrate the potential of this methodology in evaluating potential caveats of viral immune-evasion strategies and improving the design oncolytic viruses.

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Section: Resultssupporting

confidence: 88%

Model-based rational design of an oncolytic virus with improved therapeutic potential

et al. 2013

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“…VSV is a Vesiculovirus of the family Rhabdoviridae with a negative-sense RNA genome (16,17). VSV is a preferred candidate as a platform for oncolytic virus development against a variety of cancers (10,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), primarily due to its very broad tropism infecting a wide variety of animals and different cells, its short replication cycle, and high sensitivity to host interferon-mediated antiviral activity (28)(29)(30)(31)(32)(33)(34)(35). Tumor-selective tropism can be further enhanced by mutating the M protein or engineering the virus to encode beta interferon (IFN-␤).…”

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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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“…We discovered that myxoma virus (MYXV) was oncolytic for several human cancers (5,(13)(14)(15)(16). It is promising for human therapy because its genome has been sequenced, it is simple to engineer, its natural tropism is highly restricted to European rabbits (Oryctolagus cuniculus), and there is no acquired viral immunity in humans (17).…”

Section: Introductionmentioning

confidence: 99%

“…Few have used immunocompetent models (23)(24)(25)(26). We have reported promising efficacy of MYXV in immunocompromised brain tumor models (5,14,15); there is one report of MYXV in an immunocompetent model of melanoma (16). The evaluation of an oncolytic virus in immunocompetent setting is important because both the innate and the acquired immune system may dramatically modulate oncolytic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin

et al. 2010

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Oncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of MYXV in immunocompetent racine glioma models. Here, we report that MYXV infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. Intratumoral administration of MYXV with rapamycin improved viral replication in the tumor and significantly prolonged host survival. Similarly, coadministration via a method of convection-enhanced delivery (CED) enhanced viral replication and efficacy in vivo. Mechanisms by which rapamycin improved MYXV oncolysis included an inhibition of type I IFN production in vitro and a reduction of intratumoral infiltration of CD68 + microglia/macrophages and CD163 + macrophages in vivo. Our findings define a method to improve MYXV efficacy against gliomas by rapamycin coadministration, which acts to promote immune responses engaged by viral delivery. CancerRes; 70(2); 598-608. ©2010 AACR.

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Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors

Cited by 52 publications

References 44 publications

Model-based rational design of an oncolytic virus with improved therapeutic potential

Model-based rational design of an oncolytic virus with improved therapeutic potential

Vesiculovirus Neutralization by Natural IgM and Complement

Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin

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