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


Authors: Stiles, B. M.; Adusumilli, P. S.; Bhargava, A.; Stanziale, S. F.; Kim, T. H.; Chan, M. K.; Huq, R.; Wong, R.; Rusch, V. W.; Fong, Y.
Article Title: Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer
Abstract: Herpes simplex virus-1 (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. 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. 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. 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. © 2006 Nature Publishing Group All rights reserved.
Keywords: controlled study; protein expression; unclassified drug; human cell; cancer localization; nonhuman; flow cytometry; sensitivity and specificity; mouse; animals; mice; animal tissue; green fluorescent protein; animal experiment; antineoplastic activity; cancer cell culture; in vitro study; tumor cells, cultured; time factors; viral gene delivery system; animalia; mus musculus; genetic vectors; cancer invasion; cancer inhibition; genetic engineering; nude mouse; mice, nude; gene therapy; herpesviridae; simplexvirus; green fluorescent proteins; minimally invasive surgery; fluorescence microscopy; bronchoscopy; targeted therapy; herpesvirus 1, human; virus replication; fluorescence analysis; virus strain; herpes simplex virus 1; herpes; minimally invasive; sodium chloride; pleural neoplasms; thoracoscopy; cancer cell destruction; virus protein; fluorometry; pleura cancer; pleura metastasis; enhanced green fluorescent protein; nv 1066; in vivo culture; stereomicroscopy; viral gene therapy; lung neoplasm; human herpesvirus 1; herpesvirus vector; virus plaque; lung weight; virus morphogenesis
Journal Title: Cancer Gene Therapy
Volume: 13
Issue: 1
ISSN: 0929-1903
Publisher: Nature Publishing Group  
Date Published: 2006-01-01
Start Page: 53
End Page: 64
Language: English
DOI: 10.1038/sj.cgt.7700860
PUBMED: 16037824
PROVIDER: scopus
PMCID: PMC1351128
DOI/URL:
Notes: --- - "Cited By (since 1996): 16" - "Export Date: 4 June 2012" - "CODEN: CGTHE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Valerie W Rusch
    657 Rusch
  2. Richard J Wong
    230 Wong
  3. Yuman Fong
    745 Fong
  4. Mei-Ki Chan
    25 Chan
  5. Brendon Stiles
    25 Stiles
  6. Tae-Hee Kim
    5 Kim
  7. Rumana Huq
    6 Huq