title: Defective herpes simplex virus vectors expressing thymidine kinase for the treatment of malignant glioma.
abstract: Viral vectors used for cancer gene therapy have usually been either replication-incompetent vectors expressing a gene product that leads to the destruction of the tumor or replication-competent vectors that are inherently cytotoxic to the tumor cells. We have sought to combine the attributes of these different approaches using a defective herpes simplex virus (HSV) vector that consists of a defective particle, containing tandem repeats of the HSV thymidine kinase (TK) gene, and a replication-competent, non-neurovirulent HSV mutant as a helper virus. HSV-TK activity in defective vector-infected cells was significantly greater than that in helper virus-infected cells which contained a single copy of HSV-TK. Infection of cells with this defective vector renders them, as well as surrounding uninfected cells, sensitive to killing by ganciclovir. Ganciclovir treatment of C57BL/6 mice bearing TK-defective vector/helper virus-infected subcutaneous GL261 gliomas resulted in significantly decreased tumor size.
authors.affiliation: Department of Neurosurgery, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: S
authors.initials: S
authors.lastname: Miyatake
authors.forename: R L
authors.initials: RL
authors.lastname: Martuza
authors.forename: S D
authors.initials: SD
authors.lastname: Rabkin
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000235:genetics / Q000628:therapy; D018139:Simplexvirus; D013937:Thymidine Kinase / Q000235:genetics* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D013937:Thymidine Kinase