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Updated: Oct 2, 2026
Modeling Brain Tumors In Vivo Using Electroporation-Based Delivery of Plasmid DNA Representing Patient Mutation Signatures
Published on: June 23, 2023
Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors
Tatsuya Abe1, Hiroaki Wakimoto, Robert Bookstein
1Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Abstract:
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.
Insights
Intra-arterial delivery of p53-containing adenoviral vectors showed promise for treating brain tumors in rats, effectively reducing tumor size. Long-term control may require repeated treatments for sustained efficacy.
Area of Science:
- Neuro-oncology
- Gene Therapy
- Oncolytic Virotherapy
Background:
- Brain tumors pose significant treatment challenges due to the blood-brain barrier.
- Intravascular gene delivery offers a potential strategy to overcome these barriers.
Purpose of the Study:
- To assess the feasibility of intravascular adenoviral vector delivery for brain tumors.
- To evaluate the impact of tumor characteristics on gene transduction efficacy.
- To determine the therapeutic potential of p53-encoding adenoviral vectors.
Main Methods:
- Human tumor xenografts in athymic rat brains were utilized.
- Adenoviral vectors carrying LacZ (control) or p53 were administered intra-arterially.
- Tumor size, number, and transgene expression were analyzed.
- Mannitol was used to enhance vector delivery.
Main Results:
- Five-day-old tumors were optimal for adenoviral vector transduction and transgene expression.
- Intra-arterial mannitol improved transduction efficiency.
- Tumor location was a critical factor, while tumor burden had minimal impact.
- Intra-arterial p53 adenoviral vector administration significantly retarded tumor growth at 3 days.
Conclusions:
- Intra-arterial adenoviral vector delivery is a feasible approach for brain tumors.
- p53 gene therapy via this route shows initial efficacy in reducing tumor size.
- Sustained tumor growth control may necessitate multiple adenoviral treatments.
