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


CONCLUSIONS
NV1066 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.
Stiles
Brendon M
BM
Department of Surgery, the Hepatobiliary Division and the Thoracic Division, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Bhargava
Amit
A
Adusumilli
Prasad S
PS
Stanziale
Stephen F
SF
Kim
Teresa H
TH
Rusch
Valerie W
VW
Fong
Yuman
Y
D000230:Adenocarcinoma / Q000628:therapy* / Q000821:virology*; D003588:Cytopathogenic Effect, Viral; D004938:Esophageal Neoplasms / Q000628:therapy* / Q000821:virology*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006561:Herpes Simplex / Q000175:diagnosis; D006801:Humans; D007202:Indicators and Reagents; D010535:Laparoscopy; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D018139:Simplexvirus / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019562:Viral Load; D018406:Virus Physiological Phenomena; D014779:Virus Replication; D014780:Viruses
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins