Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses Journal Article

Authors: Adusumilli, P. S.; Stiles, B. M.; Chan, M. K.; Mullerad, M.; Eisenberg, D. P.; Ben-Porat, L.; Huq, R.; Rusch, V. W.; Fong, Y.
Article Title: Imaging and therapy of malignant pleural mesothelioma using replication-competent herpes simplex viruses
Abstract: Background: Malignant pleural mesothelioma (MPM) is an aggressive cancer that is refractory to current treatment modalities. Oncolytic herpes simplex viruses (HSV) used for gene therapy are genetically engineered, replication-competent viruses that selectively target tumor cells while sparing normal host tissue. The localized nature, the potential accessibility and the relative lack of distant metastasis make MPM a particularly suitable disease for oncolytic viral therapy. Methods: The infectivity, selective replication, vector spread and cytotoxic ability of three oncolytic HSV: G207, NV1020 and NV1066, were tested against eleven pathological types of MPM cell lines including those that are resistant to radiation therapy, gemcitabine or cisplatin. The therapeutic efficacy and the effect on survival of NV1066 were confirmed in a murine MPM model. Results: All three oncolytic HSV were highly effective against all the MPM cell lines tested. Even at very low concentrations of MOI 0.01 (MOI: multiplicity of viral infection, ratio of viral particles per cancer cell), HSV were highly effective against MPM cells that are resistant to radiation, gemcitabine and cisplatin. NV1066, an oncolytic HSV that expresses green fluorescent protein (GFP), was able to delineate the extent of the disease in a murine model of MPM due to selective infection and expression of GFP in tumor cells. Furthermore, NV1066 was able to reduce the tumor burden and prolong survival even when treatment was at an advanced stage of the disease. Conclusion: These findings sup port the continued investigation of oncolytic HSV as potential therapy for patients with therapy-resistant MPM. Copyright © 2006 John Wiley & Sons, Ltd.
Keywords: cancer survival; controlled study; human cell; cisplatin; advanced cancer; drug efficacy; nonhuman; gemcitabine; antineoplastic agent; mouse; animals; mice; tumor volume; green fluorescent protein; animal experiment; animal model; antineoplastic activity; cancer cell culture; cell line, tumor; strain difference; genetic vectors; cancer resistance; survival time; mice, nude; gene therapy; oncolytic virus; murinae; simplexvirus; pleura mesothelioma; mesothelioma; transplantation, heterologous; radiosensitivity; green fluorescent proteins; fluorescence microscopy; virus replication; neoplasm transplantation; virus strain; herpes simplex virus; pleural neoplasms; thoracoscopy; concentration response; nv1066; virus expression; viral gene therapy; replication competent viruses
Journal Title: Journal of Gene Medicine
Volume: 8
Issue: 5
ISSN: 1099-498X
Publisher: John Wiley & Sons  
Date Published: 2006-05-01
Start Page: 603
End Page: 615
Language: English
DOI: 10.1002/jgm.877
PUBMED: 16475242
PROVIDER: scopus
PMCID: PMC1804293
Notes: --- - "Cited By (since 1996): 22" - "Export Date: 4 June 2012" - "CODEN: JGMEF" - "Source: Scopus"
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MSK Authors
  1. Valerie W Rusch
    655 Rusch
  2. Yuman Fong
    745 Fong
  3. Mei-Ki Chan
    25 Chan
  4. Brendon Stiles
    25 Stiles
  5. Rumana Huq
    6 Huq