Targeting and Killing of Metastatic Cells in the Transgenic Adenocarcinoma of Mouse Prostate Model With Vesicular Stomatitis Virus

Moussavi, Maryam; Tearle, Howard; Fazli, Ladan; Bell, John C.; Jia, William; Rennie, Paul S.

doi:10.1038/mt.2012.285

Cited by 11 publications

(7 citation statements)

References 45 publications

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“…4 to 7). VSV replication in normal murine prostates has been observed following intraprostatic inoculation in vivo (47,48). However, the virus was quickly cleared in vivo, and there did not appear to be damage to the normal prostatic epithelium.…”

Section: Discussionmentioning

confidence: 99%

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

Puckett

Antinozzi

et al. 2015

J Virol

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A major challenge to oncolytic virus therapy is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type. Variability in response may arise due to differences in the initial genetic lesions leading to cancer development. Alternatively, susceptibility to viral oncolysis may change during cancer progression. These hypotheses were tested using cells from a transgenic mouse model of prostate cancer infected with vesicular stomatitis virus (VSV). Primary cultures from murine cancers derived from prostate-specific Pten deletion contained a mixture of cells that were susceptible and resistant to VSV. Castration-resistant cancers contained a higher percentage of susceptible cells than cancers from non- T here has been a great deal of progress in the development of new replication-competent viruses that kill cancer cells (oncolytic viruses), in understanding their mechanisms of oncolysis, and in their advancement to clinical trials (1-3). The key biological underpinning of oncolytic virus therapy is that activation of proliferative signaling pathways in cancer cells often leads to downregulation of antiviral pathways, making cancer cells more susceptible to virus infection than normal cells (4-7). Vesicular stomatitis virus (VSV) is a well-established example of a highly cytolytic virus with a tropism for cancers that have downregulated their antiviral responses (5). Our laboratory and others have made a variety of genetic modifications to enhance the selectivity of VSV for cancers versus normal tissues (7-14). For example, viruses with mutations in the viral M protein, which is responsible for suppressing host antiviral responses, are defective in their ability to invade normal tissues (15, 16) but effectively infect cancers that are defective in their antiviral responses (3). Genetically engineered VSV is currently in a phase I clinical trial for localized treatment of hepatocellular carcinoma (2). However, one of the major challenges to oncolytic virus therapy is that individual cancer cell lines vary dramatically in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type (7,13,(17)(18)(19)(20)(21)(22). The experiments presented here address the origin of these differences in susceptibility to oncolytic VSV among prostate cancers.Human prostate cancer develops as normal prostate epithelium acquires a series of mutations and epigenetic changes that lead to invasive adenocarcinoma of the prostate (23). Further mutations lead to development of metastatic prostate cancer that spreads to other organs. For patients with localized prostate cancer, radiation therapy and/or radical prostatectomy typically achieve Ͼ90% disease-free survival within 5 years (24, 25). How-

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Section: Discussionmentioning

confidence: 99%

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

Puckett

Antinozzi

et al. 2015

J Virol

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“…Oncolytic viral therapy has reemerged with potentially potent efficacy in several malignancies [21–25, 35–39]. OVs exploit the replicating machinery of the cancer cell to generate a continuous supply of virions that propagate the apoptotic infection.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, engineering VSV to code for IFN-β attenuates the effect of the virus by inducing an antiviral state in normal cells surrounding malignant cells [34]. VSV antitumor activity has been demonstrated in cancers of the ovary [23], prostate [35], head and neck [36], and colon [37], melanoma [38], and hepatocellular carcinoma [39]. …”

Section: Introductionmentioning

confidence: 99%

Oncolytic measles and vesicular stomatitis virotherapy for endometrial cancer

Liu

Steele

Suksanpaisan

et al. 2014

Gynecologic Oncology

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Objective Current adjuvant therapy for advanced-stage, recurrent, and high-risk endometrial cancer (EC) has not reduced mortality from this malignancy, and novel systemic therapies are imperative. Oncolytic viral therapy has been shown to be effective in the treatment of gynecologic cancers, and we investigated the in vitro and in vivo efficacy of the Edmonston strain of measles virus (MV) and vesicular stomatitis virus (VSV) on EC. Methods Human EC cell lines (HEC-1-A, Ishikawa, KLE, RL95-2, AN3 CA, ARK-1, ARK-2, and SPEC-2) were infected with Edmonston strain MV expressing the thyroidal sodium iodide symporter, VSV expressing either human or murine IFN-β, or recombinant VSV with a methionine deletion at residue 51 of the matrix protein and expressing the sodium iodide symporter. Xenografts of HEC-1-A and AN3 CA generated in athymic mice were treated with intratumoral MV or VSV or intravenous VSV. Results In vitro, all cell lines were susceptible to infection and cell killing by all 3 VSV strains except KLE. In addition, the majority of EC cell lines were defective in their ability to respond to type I IFN. Intratumoral VSV–treated tumors regressed more rapidly than MV-treated tumors, and intravenous VSV resulted in effective tumor control in 100% of mice. Survival was significantly longer for mice treated with any of the 3 VSV strains compared with saline. Conclusion VSV is clearly more potent in EC oncolysis than MV. A phase 1 clinical trial of VSV in EC is warranted.

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“…Vesicular stomatitis virus (VSV) Vesicular stomatitis virus, a member of rhabdovirus family, 189 is a highly promising agent for cancer treatment, since it selectively infects and kills cancer cells. 128 Recognition of this single stranded RNA virus by the Drosophila pattern recognition receptor Toll-7, similarly to mammalian TLR7, 130 results in the activation of antiviral autophagy, which is NFκB-independent. 129 Consistent with this, flies deficient for Toll-7 are more susceptible to VSV infection.…”

Section: Sindbis Virus (Sinv)mentioning

confidence: 99%

Human pathogenic bacteria, fungi, and viruses inDrosophila

2014

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Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.

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Targeting and Killing of Metastatic Cells in the Transgenic Adenocarcinoma of Mouse Prostate Model With Vesicular Stomatitis Virus

Cited by 11 publications

References 45 publications

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer

Oncolytic measles and vesicular stomatitis virotherapy for endometrial cancer

Human pathogenic bacteria, fungi, and viruses inDrosophila

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