Adeno-associated viral vector gene transfer into leptomeningeal xenografts

Leptomeningeal carcinomatosis is a painful and debilitating complicationof cancer. Indwelling reservoirs provide continuous assess tothe subarachnoid space, making leptomeningeal cancer potentially amenableto gene therapy. Adeno-associated virus (AAV) is adefective virus not associated with any human disease.We used an AAV vector to transduce medulloblastoma(DAOY) cells in a nude rat model ofleptomeningeal disease. After intraventricular injection of vector carryingthe bacterial lacZ gene, β-galactosidase positive cells werefound in the implanted tumor and in ependymaland subependymal cells but not in underlying normalbrain parenchyma. No evidence of virally-mediated toxicity wasnoted in the animals. The results of thispilot study demonstrate that AAV vectors may beused to transfer and express foreign genes inestablished leptomeningeal tumors.