Controlling brain tumor growth by intraventricular administration of an AAV vector encoding IFN-beta.
Glioblastoma multiforme (GBM) is the most aggressive type of all primary brain tumors, with an overall median survival <1 year after diagnosis. Despite introduction of multimodal treatment approaches, the prognosis has not improved significantly over the past 50 years. In this study we investigated the effect of intracerebroventricular (ICV) injection of an adeno-associated virus (AAV) vector encoding human interferon-beta (AAV-hIFN-beta) on glioblastoma growth. Recently, we found that peritumoral parenchymal transduction with an AAV-hIFN-beta was exceptionally efficient in eradicating GBM brain tumors. However, the extensive infiltration and migration displayed by glioblastoma cells in patients may leave a significant number of tumor cells outside a local therapeutic zone created by intraparenchymal delivery of AAV vectors. Here we show that pretreatment of mice by ICV infusion of an AAV-IFN-beta completely prevents tumor growth in an orthotopic model of GBM. Furthermore, ICV infusion of AAV-IFN-beta into mice bearing preestablished U87 intracranial tumors improved their survival compared to mice infused through the same route with a control AAV vector. These data suggest that ICV injection of AAV vectors encoding antitumor proteins is a promising approach deserving further consideration for the treatment of GBM.
Meijer
D H
DH
Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Maguire
C A
CA
LeRoy
S G
SG
Sena-Esteves
M
M
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007276:Injections, Intraventricular; D016899:Interferon-beta / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation
D016899:Interferon-beta