A third-generation herpesvirus is effective against gastroesophageal cancer Journal Article

Authors: Wong, J.; Kelly, K.; Mittra, A.; González, S. J.; Song, K. Y.; Simpson, G.; Coffin, R.; Fong, Y.
Article Title: A third-generation herpesvirus is effective against gastroesophageal cancer
Abstract: Background: Gastroesophageal cancer remains a leading cause of cancer deaths and is uniformly fatal in patients presenting with metastases and recurrence. This study sets out to determine the effect of a third-generation, replication-competent, oncolytic herpes simplex type 1 virus containing transgenes encoding for a fusogenic membrane glycoprotein and Fcy::Fur, against gastroesophageal cancer. Methods: The cytotoxic effect of the virus was tested on human gastroesophageal cancer cell lines OCUM-2MD3, MKN-45, AGS, MKN-1, MKN-74, and BE-3 at sequential multiplicities of infection (MOI). Cytotoxicity was measured using a lactate dehydrogenase assay. Viral replication was tested by serially diluting supernatants from viral infections and titering on VERO cells via standard plaque assay. Correlations of cytotoxicity and viral replication were also investigated. Results: All cell lines were susceptible to viral infection and demonstrated a dose-dependent effect, with greater and faster cytotoxicity at higher MOIs. Viral replication was supported in the cell lines tested, with peak titers by d 5, some supporting as high as >40,000× amplification. Cell lines with longer doubling times (>30 h) also achieved higher viral titers at a MOI of 0.1. Cell lines with shorter doubling times achieved 50% cell kill in fewer days, with an average of 2.3 d for cell lines with doubling times under 30 h compared with 4.4 d for cell lines with doubling times over 30 h. Conclusion: These results suggest that this third-generation oncolytic herpesvirus can effectively infect and lyse gastroesophageal cancer cells and may provide a novel therapy against gastroesophageal cancer. © 2010 Elsevier Inc. All rights reserved.
Keywords: human cell; dose response; antineoplastic activity; cancer cell culture; cytotoxicity; cell line, tumor; human cell culture; oncolytic virus; oncolytic virotherapy; stomach cancer; herpesvirus 1, human; virus replication; esophageal adenocarcinoma; stomach adenocarcinoma; herpes simplex virus 1; stomach neoplasms; esophageal neoplasms; vero cell; oncolytic; gastroesophageal cancer; herpesvirus
Journal Title: Journal of Surgical Research
Volume: 163
Issue: 2
ISSN: 0022-4804
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 2010-10-01
Start Page: 214
End Page: 220
Language: English
DOI: 10.1016/j.jss.2010.03.021
PUBMED: 20538290
PROVIDER: scopus
PMCID: PMC3266820
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: JSGRA" - "Source: Scopus"
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MSK Authors
  1. Kaitlyn J Kelly
    28 Kelly
  2. Kyo Young Song
    3 Song
  3. Yuman Fong
    745 Fong
  4. Arjun Mittra
    8 Mittra
  5. Joyce Wong
    16 Wong