The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer

Stiles, Brendon M.; Bhargava, Amit; Adusumilli, Prasad S.; Stanziale, Stephen F.; Kim, Teresa H.; Rusch, Valerie W.; Fong, Yuman

doi:10.1067/msy.2003.244

Cited by 37 publications

(29 citation statements)

References 15 publications

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“…A previous study from our laboratory has demonstrated the ability of NV1066 to replicate in vivo in murine flank tumors (28). Viral titers increase over time as measured by real-time PCR for viral genomic DNA, with a large replication burst evident between 24-48 hours.…”

Section: Time Course Of In Vivo Egfp Expressionmentioning

confidence: 92%

“…Eighty-six percent of patients diagnosed with lung cancer die within 5 years(2). Herpes simplex virus mediated oncolysis and gene therapy have emerged as promising treatment modalities against cancer (3)(4)(5)(6)(7)(8)(9)(10). Oncolysis results from the replicative life cycle of the virus, which lyses infected cells for release of viral progeny.…”

Section: Introductionmentioning

confidence: 99%

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Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer

et al. 2005

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Purpose-Herpes simplex virus-one (HSV-1) oncolytic therapy and gene therapy are promising treatment modalities against cancer. NV1066, one such HSV-1 virus carries a marker gene for enhanced green fluorescent protein (EGFP). The purpose of this study was to determine whether NV1066 is cytotoxic to lung cancer and whether EGFP is a detectable marker of viral infection in vitro and in vivo. We further investigated whether EGFP expression in infected cells can be used to localize the virus and to identify small metastatic tumor foci (< 1 mm.) in vivo by means of minimally invasive endoscopic systems equipped with fluorescent filters.Experimental Design-In A549 human lung cancer cells, in vitro viral replication was determined by plaque assay, cell kill by LDH release assay, and EGFP expression by flow cytometry. In vivo, A549 cells were injected into the pleural cavity of athymic mice. Mice were treated with intrapleural injection of NV1066 or saline and examined for EGFP expression in tumor deposits using a stereomicroscope or a fluorescent thoracoscopic system. Results-NV1066 replicated in, expressed EGFP in infected cells and killed tumor cells in vitro.In vivo, treatment with intrapleural NV1066 decreased pleural disease burden, as measured by chest wall nodule counts and organ weights. EGFP was easily visualized in tumor deposits, including microscopic foci, by fluorescent thoracoscopy.Conclusions-NV1066 has significant oncolytic activity against a human NSCLC cell line and is effective in limiting the progression of metastatic disease in an in vivo orthotopic model. By incorporating fluorescent filters into endoscopic systems, a minimally-invasive means for diagnosing small metastatic pleural deposits and localization of viral therapy for thoracic malignancies may be developed using the EGFP marker gene inserted in oncolytic herpes simplex viruses.

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Section: Time Course Of In Vivo Egfp Expressionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer

et al. 2005

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“…NV1066 infection was carried out at multiplicities of infection (MOI: number of viral plaque forming units per tumor cell) of 0.1, 0.2, 0.3, 0.4 or 0.5 in a total volume of 100 μl of medium. Combination therapy was performed using serial dilutions of RT (2,4,6,8, and 10 Gy) and NV1066 (MOI 0.1, 0.2, 0.3, 0.4 and 0.5) in a 1:20 ratio for both cell lines. These ratios were determined by estimating the LD 50 for each therapy in initial experiments and by using these doses to determine the ratio of combination therapy.…”

Section: In Vitro Cytotoxicity Assaymentioning

confidence: 99%

“…Herpes simplex virus (HSV) mediated oncolysis and gene therapy have emerged as promising treatment modalities against cancer (6)(7)(8)(9)(10)(11). Oncolysis results from the replicative life cycle of the virus, which lyses infected tumor cells and releases viral progeny for further infection and killing of neighboring cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer

Adusumilli¹,

Stiles²,

Chan³

et al. 2005

The Annals of Thoracic Surgery

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Background-Replication-competent oncolytic herpes simplex viruses (HSV) with deletion of the γ 1 34.5 gene preferentially replicate in and kill malignant cells. γ 1 34.5 codes for ICP 34.5, a protein that enhances viral replication, and is homologous to Growth Arrest and DNA damage Protein 34 (GADD34), a radiation-inducible DNA repair gene. We hypothesized that radiation therapy may potentiate efficacy of oncolytic viral therapy by up-regulating GADD 34 and promoting viral replication.

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“…A number of studies from our group and others have determined that these viruses are highly specific for tumor cells while sparing normal cells (13)(14)(15)(16)(17)(18)(19)(20)(21). Oncolytic HSV therapy has shown to be effective against multiple tumor types including lung, esophageal, gastric, colorectal, gallbladder, hepatic, pancreatic, bladder cancer and mesothelioma (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Given the specificity of herpes viral replication for tumor cells, we sought to determine whether NV1066, a HSV-1 mutant virus used in this study can delineate tumor tissue from normal tissue.…”

Section: Introductionmentioning

confidence: 99%

Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging

et al. 2006

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The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer

Cited by 37 publications

References 15 publications

Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer

Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer

Radiation Therapy Potentiates Effective Oncolytic Viral Therapy in the Treatment of Lung Cancer

Virally-directed fluorescent imaging (VFI) can facilitate endoscopic staging

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