title: Adeno-associated viral vector gene transfer into leptomeningeal xenografts.
abstract: Leptomeningeal carcinomatosis is a painful and debilitating complication of cancer. Indwelling reservoirs provide continuous assess to the subarachnoid space, making leptomeningeal cancer potentially amenable to gene therapy. Adeno-associated virus (AAV) is a defective virus not associated with any human disease. We used an AAV vector to transduce medulloblastoma (DAOY) cells in a nude rat model of leptomeningeal disease. After intraventricular injection of vector carrying the bacterial lacZ gene, beta-galactosidase positive cells were found in the implanted tumor and in ependymal and subependymal cells but not in underlying normal brain parenchyma. No evidence of virally-mediated toxicity was noted in the animals. The results of this pilot study demonstrate that AAV vectors may be used to transfer and express foreign genes in established leptomeningeal tumors.
authors.affiliation: Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Rosenfeld
authors.forename: I
authors.initials: I
authors.lastname: Bergman
authors.forename: L
authors.initials: L
authors.lastname: Schramm
authors.forename: J A
authors.initials: JA
authors.lastname: Griffin
authors.forename: M G
authors.initials: MG
authors.lastname: Kaplitt
authors.forename: P I
authors.initials: PI
authors.lastname: Meneses
mesh_terms: D017500:Adenovirus E1A Proteins / Q000096:biosynthesis; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis; D002460:Cell Line; D002528:Cerebellar Neoplasms / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007276:Injections, Intraventricular; D007668:Kidney; D008527:Medulloblastoma / Q000473:pathology / Q000628:therapy*; D008577:Meningeal Neoplasms / Q000473:pathology / Q000628:therapy*; D051381:Rats; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D013346:Subarachnoid Space; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
chemical_list: D017500:Adenovirus E1A Proteins; D000957:Antigens, Viral, Tumor; D011994:Recombinant Proteins; D001616:beta-Galactosidase