Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response Journal Article

Authors: Au, J. T.; Mittra, A.; Song, T. J.; Cavnar, M.; Jun, K.; Carson, J.; Gholami, S.; Haddad, D.; Gaujoux, S.; Monette, S.; Ezell, P.; Wolchok, J.; Fong, Y.
Article 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%. 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. © 2013 Mosby, Inc. All rights reserved.
Keywords: controlled study; human tissue; dose response; drug dose comparison; nonhuman; flow cytometry; laparotomy; neoplasms; cell proliferation; protein blood level; animals; bone marrow; granulocyte macrophage colony stimulating factor; animal experiment; lymph node; electroporation; plasmids; bone marrow cell; tissue level; macrophage; swine; plasmid vector; nonviral gene delivery system; gene transfer techniques; granulocyte-macrophage colony-stimulating factor; irreversible electroporation; experimental pig; liver level; genetic therapy
Journal Title: Surgery
Volume: 154
Issue: 3
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 2013-09-01
Start Page: 496
End Page: 503
Language: English
DOI: 10.1016/j.surg.2013.06.005
PROVIDER: scopus
PUBMED: 23972655
PMCID: PMC4140181
Notes: --- - "Export Date: 1 October 2013" - "CODEN: SURGA" - "Source: Scopus"
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MSK Authors
  1. Jedd D Wolchok
    665 Wolchok
  2. Michael Joseph Cavnar
    27 Cavnar
  3. Yuman Fong
    745 Fong
  4. Dana Haddad
    18 Haddad
  5. Sepideh Gholami
    27 Gholami
  6. Kyonghwa Jun
    3 Jun
  7. Sebastien Monette
    76 Monette
  8. Taejin Song
    7 Song
  9. Joyce Au
    12 Au
  10. Sebastien Gaujoux
    10 Gaujoux
  11. Paula Cherie Ezell
    19 Ezell
  12. Joshua S Carson
    12 Carson
  13. Arjun Mittra
    8 Mittra