title: Antitumor effects on human melanoma xenografts of an amplicon vector transducing the herpes thymidine kinase gene followed by ganciclovir.
abstract: Herpes simplex virus type-1 (HSV-1) has been demonstrated as a potentially useful gene delivery vector for gene therapy due to its high efficiency of in vivo transduction. The helper virus-dependent, HSV- 1 amplicon vectors were developed for easier operation and their larger capacity. In this study, the herpes simplex virus type-1 thymidine kinase (HSVtk) gene was cloned into the pHE700 amplicon vector to make an HE7tk vector and used for in vivo gene delivery. Human melanoma xenografts were established in athymic nude mice. Tumors were injected directly with HE7tk vector alone, HE7tk vector followed by ganciclovir (GCV), or a pHE700 amplicon vector carrying a green fluorescent protein (HE7GFP) gene followed by GCV. Efficient HSVtk transgene expression was found in the tumor 3 days after injection. Animals transduced with HE7tk followed by GCV had minimal tumor growth (P < .01 ). Animals that received either HE7tk vector without GCV or HE7GFP vector with GCV had some reduction in tumor growth compared to animals that were injected with buffer only. These data indicate that replication-defective HSV-1 amplicon vectors can be used effectively to deliver transgenes into solid tumors in vivo.
authors.affiliation: Human Gene Therapy Research Institute, Iowa Methodist Medical Center, Des Moines 50309, USA.
authors.forename: Suming
authors.initials: S
authors.lastname: Wang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Qi
authors.forename: Michael
authors.initials: M
authors.lastname: Smith
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Link
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D024201:Bystander Effect; D015774:Ganciclovir / Q000627:therapeutic use*; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013937:Thymidine Kinase / Q000235:genetics*; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D013937:Thymidine Kinase; D001616:beta-Galactosidase; D015774:Ganciclovir