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

B. M. Stiles, P. S. Adusumilli, A. Bhargava, S. F. Stanziale, T. H. Kim, M. K. Chan, R. Huq, R. Wong, V. W. Rusch, Y. Fong

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)53-64
Number of pages12
JournalCancer Gene Therapy
Volume13
Issue number1
DOIs
StatePublished - Jan 2006

Fingerprint

Herpes Simplex
Neoplasms
Human Herpesvirus 1
Therapeutics
Lung Neoplasms
Oncolytic Viruses
Pleural Diseases
Viruses
Pleural Cavity
Thoracoscopy
Organ Size
enhanced green fluorescent protein
Thoracic Wall
Virus Diseases
Simplexvirus
Nude Mice
Genetic Therapy
Genes
Disease Progression
Flow Cytometry

Keywords

  • Bronchoscopy
  • Green fluorescent protein
  • Lung neoplasm
  • Minimally invasive
  • Targeted therapy
  • Thoracoscopy

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Stiles, B. M., Adusumilli, P. S., Bhargava, A., Stanziale, S. F., Kim, T. H., Chan, M. K., ... Fong, Y. (2006). Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer. Cancer Gene Therapy, 13(1), 53-64. https://doi.org/10.1038/sj.cgt.7700860

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

In: Cancer Gene Therapy, Vol. 13, No. 1, 01.2006, p. 53-64.

Research output: Contribution to journalArticle

Stiles, BM, Adusumilli, PS, Bhargava, A, Stanziale, SF, Kim, TH, Chan, MK, Huq, R, Wong, R, Rusch, VW & Fong, Y 2006, 'Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer', Cancer Gene Therapy, vol. 13, no. 1, pp. 53-64. https://doi.org/10.1038/sj.cgt.7700860
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. / Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer. In: Cancer Gene Therapy. 2006 ; Vol. 13, No. 1. pp. 53-64.
@article{649d8d63042c4d539cd519bcdba82b03,
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.",
keywords = "Bronchoscopy, Green fluorescent protein, Lung neoplasm, Minimally invasive, Targeted therapy, Thoracoscopy",
author = "Stiles, {B. M.} and Adusumilli, {P. S.} and A. Bhargava and Stanziale, {S. F.} and Kim, {T. H.} and Chan, {M. K.} and R. Huq and R. Wong and Rusch, {V. W.} and Y. Fong",
year = "2006",
month = "1",
doi = "10.1038/sj.cgt.7700860",
language = "English (US)",
volume = "13",
pages = "53--64",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Minimally invasive localization of oncolytic herpes simplex viral therapy of metastatic pleural cancer

AU - Stiles, B. M.

AU - Adusumilli, P. S.

AU - Bhargava, A.

AU - Stanziale, S. F.

AU - Kim, T. H.

AU - Chan, M. K.

AU - Huq, R.

AU - Wong, R.

AU - Rusch, V. W.

AU - Fong, Y.

PY - 2006/1

Y1 - 2006/1

N2 - 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.

AB - 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.

KW - Bronchoscopy

KW - Green fluorescent protein

KW - Lung neoplasm

KW - Minimally invasive

KW - Targeted therapy

KW - Thoracoscopy

UR - http://www.scopus.com/inward/record.url?scp=29144511487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29144511487&partnerID=8YFLogxK

U2 - 10.1038/sj.cgt.7700860

DO - 10.1038/sj.cgt.7700860

M3 - Article

C2 - 16037824

AN - SCOPUS:29144511487

VL - 13

SP - 53

EP - 64

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 1

ER -