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.
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 humangastroesophageal 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.
Authors: Joseph J Bennett; Keith A Delman; Bryan M Burt; Adam Mariotti; Sandeep Malhotra; Jonathan Zager; Henrik Petrowsky; Stephen Mastorides; Howard Federoff; Yuman Fong Journal: Cancer Gene Ther Date: 2002-11 Impact factor: 5.987
Authors: Y Hippo; M Yashiro; M Ishii; H Taniguchi; S Tsutsumi; K Hirakawa; T Kodama; H Aburatani Journal: Cancer Res Date: 2001-02-01 Impact factor: 12.701
Authors: B L Liu; M Robinson; Z-Q Han; R H Branston; C English; P Reay; Y McGrath; S K Thomas; M Thornton; P Bullock; C A Love; R S Coffin Journal: Gene Ther Date: 2003-02 Impact factor: 5.250
Authors: Jiafu Ji; Xin Chen; Suet Yi Leung; Jen-Tsan A Chi; Kent Man Chu; Siu Tsan Yuen; Rui Li; Annie S Y Chan; Jiyou Li; Nina Dunphy; Samuel So Journal: Oncogene Date: 2002-09-19 Impact factor: 9.867
Authors: Howard L Kaufman; Dae Won Kim; Gail DeRaffele; Josephine Mitcham; Rob S Coffin; Seunghee Kim-Schulze Journal: Ann Surg Oncol Date: 2010-03 Impact factor: 5.344
Authors: G R Simpson; A Horvath; N E Annels; T Pencavel; S Metcalf; R Seth; P Peschard; T Price; R S Coffin; H Mostafid; A A Melcher; K J Harrington; H S Pandha Journal: Br J Cancer Date: 2012-01-12 Impact factor: 7.640
Authors: Raquel Yokoda; Bolni M Nagalo; Mansi Arora; Jan B Egan; James M Bogenberger; Thomas T DeLeon; Yumei Zhou; Daniel H Ahn; Mitesh J Borad Journal: Oncolytic Virother Date: 2018-03-23