Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors.
Human tumor xenografts established in athymic rat brains were used to determine the feasibility of intravascular delivery of tumor suppressor genes to brain tumors. Both tumor size and number were compared to characterize the effect of tumor burden on tumor transduction efficacy by a control LacZ-containing adenoviral vector. Experiments with tumors grown in vivo for either 3, 5, or 7 days demonstrated that 5-day-old tumors provided the best target for vector infection and transgene expression by this mode of administration. Intra-arterial mannitol facilitated transduction efficiency. Tumor burden did not seem to affect transduction, while tumor location appeared to be an important factor. Based on these results, intra-arterial infusion of a p53-containing adenoviral vector was carried out and resulted in significant retardation of brain tumor growth 3 days after administration. Effects at longer time points were not as significant. These findings indicate that intra-arterial administration of adenoviral vectors containing p53 is efficient and can result in changes in tumor size, but that long-term control of tumor growth may require multiple adenoviral treatments.
Abe
Tatsuya
T
Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Wakimoto
Hiroaki
H
Bookstein
Robert
R
Maneval
Daniel C
DC
Chiocca
E Antonio
EA
Basilion
James P
JP
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004234:Diuretics, Osmotic / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D018773:Genes, erbB-1 / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007763:Lac Operon / Q000502:physiology; D008353:Mannitol / Q000493:pharmacokinetics / Q000494:pharmacology; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D015996:Survival Rate; D014018:Tissue Distribution; D014161:Transduction, Genetic; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D004234:Diuretics, Osmotic; D016159:Tumor Suppressor Protein p53; D008353:Mannitol