Background
Electroporation uses an electric field to induce pores in the cell membrane that can
transfer macromolecules into target cells. Modulation of electrical parameters leads
to irreversible electroporation (IRE), which is being developed for tissue ablation.
We sought to evaluate whether the application of IRE may induce a lesser electric
field in the periphery where reversible electroporation may occur, facilitating gene
transfer of a granulocyte macrophage colony-stimulating factor (GM-CSF) plasmid to
produce its biologic response.
Methods
Yorkshire pigs underwent laparotomy, and IRE of the liver was performed during hepatic
arterial infusion of 1 or 7 mg of a naked human GM-CSF plasmid. The serum, liver,
lymph nodes, and bone marrow were harvested for analysis.
Results
Human GM-CSF level rose from undetectable to 131 pg/mL in the serum at 24 hours after
IRE and plasmid infusion. The liver demonstrated an ablation zone surrounded by an
immune infiltrate that had greater macrophage intensity than when treated with IRE
or plasmid infusion alone. This dominance of macrophages was dose dependent. Distant
effects of GM-CSF were found in the bone marrow, where proliferating myeloid cells
increased from 14% to 25%.
Conclusion
IRE facilitated gene transfer of the GM-CSF plasmid and brought about a local and
systemic biologic response. This technique holds potential for tumor eradication and
immunotherapy of residual cancer.
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Article info
Publication history
Accepted:
June 10,
2013
Identification
Copyright
© 2013 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
