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

Joyce T. Au, Arjun Mittra, Tae Jin Song, Michael Cavnar, Kyonghwa Jun, Joshua Carson, Sepideh Gholami, Dana Haddad, Sebastien Gaujoux, Sebastien Monette, Paula Ezell, Jedd Wolchok, Yuman Fong

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)496-503
    Number of pages8
    JournalSurgery (United States)
    Volume154
    Issue number3
    DOIs
    Publication statusPublished - 2013 Sep

    ASJC Scopus subject areas

    • Surgery

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