A third-generation herpesvirus is effective against gastroesophageal cancer.
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.


CONCLUSIONS
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.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Joyce
J
Wong
Kaitlyn
K
Kelly
Arjun
A
Mittra
Segundo Jaime
SJ
Gonzalez
Kyo Young
KY
Song
Guy
G
Simpson
Robert
R
Coffin
Yuman
Y
Fong
D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000628:therapy* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D050130:Oncolytic Virotherapy; D013274:Stomach Neoplasms / Q000628:therapy* / Q000821:virology; D014779:Virus Replication