title: Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer.
abstract: BACKGROUND
  There are still no effective treatments for superficial bladder cancer (SBC)/non-muscle invasive bladder cancer. Following treatment, 20% of patients still develop metastatic disease. Superficial bladder cancer is often multifocal, has high recurrences after surgical resection and recurs after intravesical live Bacillus Calmette-Guérin. Oncovex(GALV/CD), an oncolytic herpes simplex virus-1, has shown enhanced local tumour control by combining oncolysis with the expression of a highly potent pro-drug activating gene and the fusogenic glycoprotein.
  
  
  METHODS
  In vitro fusion/prodrug/apoptotic cell-based assays. In vivo orthotopic bladder tumour model, visualised by computed microtomography.
  
  
  RESULTS
  Treatment of seven human bladder carcinoma cell lines with the virus resulted in tumour cell killing through oncolysis, pro-drug activation and glycoprotein fusion. Oncovex(GALV/CD) and mitomycin C showed a synergistic effect, whereas the co-administration with cisplatin or gemcitabine showed an antagonistic effect in vitro. Transitional cell cancer (TCC) cells follow an apoptotic cell death pathway after infection with Oncovex(GALV/CD) with or without 5-FC. In vivo results showed that intravesical treatment with Oncovex(GALV/CD) + prodrug (5-FC) reduced the average tumour volume by over 95% compared with controls.
  
  
  CONCLUSIONS
  Our in vitro and in vivo results indicate that Oncovex(GALV/CD) can improve local tumour control within the bladder, and potentially alter its natural history.
authors.affiliation: Oncology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK. g.simpson@surrey.ac.uk
authors.forename: G R
authors.initials: GR
authors.lastname: Simpson
authors.forename: A
authors.initials: A
authors.lastname: Horvath
authors.forename: N E
authors.initials: NE
authors.lastname: Annels
authors.forename: T
authors.initials: T
authors.lastname: Pencavel
authors.forename: S
authors.initials: S
authors.lastname: Metcalf
authors.forename: R
authors.initials: R
authors.lastname: Seth
authors.forename: P
authors.initials: P
authors.lastname: Peschard
authors.forename: T
authors.initials: T
authors.lastname: Price
authors.forename: R S
authors.initials: RS
authors.lastname: Coffin
authors.forename: H
authors.initials: H
authors.lastname: Mostafid
authors.forename: A A
authors.initials: AA
authors.lastname: Melcher
authors.forename: K J
authors.initials: KJ
authors.lastname: Harrington
authors.forename: H S
authors.initials: HS
authors.lastname: Pandha
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor / Q000187:drug effects; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D006023:Glycoproteins; D011355:Prodrugs; D005472:Fluorouracil