Antiangiogenic Arming of an Oncolytic Vaccinia Virus Enhances Antitumor Efficacy in Renal Cell Cancer Models

Guse, Kilian; Słoniecka, Marta; Diaconu, Iulia; Ottolino‐Perry, Kathryn; Tang, Nan; Ng, Calvin S.H.; Bœuf, Fabrice Le; Bell, John C.; McCart, J. Andrea; Ristimäki, Ari; Pesonen, Sari; Cerullo, Vincenzo; Hemminki, Akseli

doi:10.1128/jvi.00692-09

Cited by 52 publications

(61 citation statements)

References 46 publications

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“…The GLAF-1-producing virus demonstrated enhanced therapeutic efficacy in targeting adult human pancreatic, lung, and prostate cancer xenografts compared to the GLV-1h68 parent virus, and the treatment effect was comparable to that seen with the parent virus combined with bevacizumab 49. Similarly, vvDD, a Western Reserve VV with deletions in TK and VV growth factor, inhibited enhanced antitumor efficacy with an antiangiogenic effect in renal cell cancer models when armed with soluble VEGF receptor 1 protein 50. Other approaches for enhanced cell killing or molecular imaging have been used including the cytosine deaminase gene as suicide gene therapy with 5-fluorocytosine or the gene expressing the human somatostatin receptor type 2 51,52…”

Section: Vaccinia Virusmentioning

confidence: 94%

Oncolytic virotherapy for pediatric malignancies: future prospects

Waters¹,

Friedman²,

Ring³

et al. 2016

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Pediatric solid tumors remain a major health concern, with nearly 16,000 children diagnosed each year. Of those, ~2,000 succumb to their disease, and survivors often suffer from lifelong disability secondary to toxic effects of current treatments. Countless multimodality treatment regimens are being explored to make advances against this deadly disease. One targeted treatment approach is oncolytic virotherapy. Conditionally replicating viruses can infect tumor cells while leaving normal cells unharmed. Four viruses have been advanced to pediatric clinical trials, including herpes simplex virus-1, Seneca Valley virus, reovirus, and vaccinia virus. In this review, we discuss the mechanism of action of each virus, pediatric preclinical studies conducted to date, past and ongoing pediatric clinical trials, and potential future direction for these novel viral therapeutics.

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Section: Vaccinia Virusmentioning

confidence: 94%

Oncolytic virotherapy for pediatric malignancies: future prospects

Waters¹,

Friedman²,

Ring³

et al. 2016

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“…Thus far, AdHSV-tk/GCV and AdsVEGFR-1 gene therapies have not been combined for the treatment of MG or any other cancer. AdHSV-tk/GCV has been successfully combined with endostatin gene therapy for the treatment of renal cell cancer (Pulkkanen et al, 2002), while sVEGFR-1 has been combined with oncolytic viruses (Zhang et al, 2005;Guse et al, 2010), other sVEGFRs (Sallinen et al, 2009), soluble Tie2 (Sallinen et al, 2011), and chemotherapy (Sopo et al, 2012). All previous studies with sVEGFR-1 gene therapy for MG were conducted on nude mouse models.…”

Section: Discussionmentioning

confidence: 99%

Soluble Vascular Endothelial Growth Factor Receptor-1 Improves Therapeutic Efficacy of Suicide Gene Therapy in an Angiogenesis-Independent Manner

et al. 2014

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Malignant gliomas (MGs) are highly vascularized, aggressive brain cancers carrying a dismal prognosis. Because of their high vascularity, anti-angiogenic therapy is a potential treatment option. Indeed, the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has demonstrated promising results in clinical trials. Similarly, adenovirus-medicated Herpes simplex virus thymidine kinase and ganciclovir (AdHSV-tk/GCV) suicide gene therapy has established itself in clinical trials as a potential novel therapeutic strategy for MGs. In this study, we demonstrate the feasibility of combining adenovirus-mediated soluble VEGF receptor-1 anti-angiogenic gene therapy with AdHSV-tk/GCV suicide gene therapy to treat experimental MGs. Our results reveal that, apart from inhibiting angiogenesis, other anti-tumor mechanisms, such as reduction of infiltration by tumor-associated macrophages/microglia, may contribute to the improved therapeutic benefit of combination therapy.

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“…Recent reports have demonstrated augmentation of antitumour efficacy of OV by manipulating vascular endothelial growth factor-mediated signalling (Guse et al , 2010; Kottke et al , 2010). In contrast, our approach involved disruption of tumour vasculature using PDT to enhance viral delivery and distribution.…”

Section: Discussionmentioning

confidence: 99%

Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

et al. 2011

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Background:Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice.Methods:The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay.Results:Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue.Conclusion:These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV.

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Antiangiogenic Arming of an Oncolytic Vaccinia Virus Enhances Antitumor Efficacy in Renal Cell Cancer Models

Cited by 52 publications

References 46 publications

Oncolytic virotherapy for pediatric malignancies: future prospects

Oncolytic virotherapy for pediatric malignancies: future prospects

Soluble Vascular Endothelial Growth Factor Receptor-1 Improves Therapeutic Efficacy of Suicide Gene Therapy in an Angiogenesis-Independent Manner

Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

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