The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer Journal Article
| Authors: | Stiles, B. M.; Bhargava, A.; Adusumilli, P. S.; Stanziale, S. F.; Kim, T. H.; Rusch, V. W.; Fong, Y. |
| Article Title: | The replication-competent oncolytic herpes simplex mutant virus NV1066 is effective in the treatment of esophageal cancer |
| Abstract: | Background. The oncolytic herpes simplex-1 virus, NV1066, is a replication-competent virus that has been engineered to infect and lyse tumor cells selectively and to carry a transgene for enhanced green fluorescent protein (EGFP). The purpose of this study was to determine viral cytotoxicity in an esophageal cancer cell line and to determine whether EGFP expression could be used as a marker of viral infection. Methods. BE3 esophageal adenocarcinoma cells were infected with NV1066 in vitro to determine cell kill and viral replication. EGFP expression was assessed by flow cytometry. The in vivo anti-tumor activity of NV1066 was tested in subcutaneous and intraperitoneal xenograft models. EGFP expression was localized in vivo by fluorescent microscopy and fluorescent laparoscopy. Results. NV1066 effectively replicated within and killed BE3 cells in vitro and in vivo. EGFP expression identified infected tumor cells. After NV1066 treatment in vivo, EGFP expression localized to the tumor. In an intraperitoneal tumor model, EGFP could be visualized endoscopically using a laparoscope with a fluorescent filter. Conclusion. NW1066 has oncolytic activity against the BE3 cell line and may be a useful therapy against esophageal cancer. EGFP expression localizes the virus and may help to identify tumor deposits in vivo. Oncolytic activity with NV1066 against gastrointestinal cancers may potentially be tracked by endoscopy. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; nonhuman; flow cytometry; laparoscopy; protein localization; adenocarcinoma; mouse; green fluorescent protein; animal experiment; animal model; herpes simplex; cancer cell culture; tumor cells, cultured; cancer model; luminescent proteins; digestive system cancer; genetic engineering; xenograft; transgene; oncolytic virus; simplexvirus; green fluorescent proteins; fluorescence microscopy; microscopy, fluorescence; virus replication; esophagus cancer; herpes simplex virus 1; esophageal neoplasms; virus mutant; cytopathogenic effect, viral; indicators and reagents; enhanced green fluorescent protein; tumor cell destruction; viral load; viruses; humans; human; male; priority journal; article; herpes simplex virus 1 nv1066; viral physiology |
| Journal Title: | Surgery |
| Volume: | 134 |
| Issue: | 2 |
| ISSN: | 0039-6060 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2003-08-01 |
| Start Page: | 357 |
| End Page: | 364 |
| Language: | English |
| DOI: | 10.1067/msy.2003.244 |
| PUBMED: | 12947341 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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