title: Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas.
abstract: We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication-competence in glioblastoma cells (and other dividing cells), attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker. G207 has deletions at both gamma 34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice harbouring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inoculation with G207 causes decreased tumour growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV-sensitive non-human primates. These results suggest that G207 should be considered for clinical evaluation in the treatment of glioblastomas.
authors.affiliation: Georgetown Brain Tumor Center, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mineta
authors.forename: S D
authors.initials: SD
authors.lastname: Rabkin
authors.forename: T
authors.initials: T
authors.lastname: Yazaki
authors.forename: W D
authors.initials: WD
authors.lastname: Hunter
authors.forename: R L
authors.initials: RL
authors.lastname: Martuza
mesh_terms: D000818:Animals; D016645:Aotidae; D001932:Brain Neoplasms / Q000628:therapy*; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D003673:Defective Viruses / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D015774:Ganciclovir / Q000494:pharmacology; D017930:Genes, Reporter; D015316:Genetic Therapy; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D015552:Injections, Intralesional; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D012449:Safety; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D013696:Temperature; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics; D017735:Virus Latency; D014779:Virus Replication; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D014764:Viral Proteins; C054366:herpes simplex virus type 1-protein ICP6; D001616:beta-Galactosidase; D015774:Ganciclovir