title: Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response.
abstract: 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%.
  
  
  CONCLUSIONS
  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.
authors: Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors: Joyce T
authors: JT
authors: Au
authors: Arjun
authors: A
authors: Mittra
authors: Tae Jin
authors: TJ
authors: Song
authors: Michael
authors: M
authors: Cavnar
authors: Kyonghwa
authors: K
authors: Jun
authors: Joshua
authors: J
authors: Carson
authors: Sepideh
authors: S
authors: Gholami
authors: Dana
authors: D
authors: Haddad
authors: Sebastien
authors: S
authors: Gaujoux
authors: Sebastien
authors: S
authors: Monette
authors: Paula
authors: P
authors: Ezell
authors: Jedd
authors: J
authors: Wolchok
authors: Yuman
authors: Y
authors: Fong
mesh_terms: D000818:Animals; D018274:Electroporation / Q000379:methods*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D010957:Plasmids; D013552:Swine
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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