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 journalArticle

8 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 (US)
Pages (from-to)496-503
Number of pages8
JournalSurgery (United States)
Volume154
Issue number3
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Electroporation
Granulocyte-Macrophage Colony-Stimulating Factor
Plasmids
Genes
Liver
Bone Marrow
Macrophages
Residual Neoplasm
Myeloid Cells
Serum
Immunotherapy
Laparotomy
Swine
Lymph Nodes
Cell Membrane

ASJC Scopus subject areas

  • Surgery

Cite this

Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response. / Au, Joyce T.; Mittra, Arjun; Song, Tae Jin; Cavnar, Michael; Jun, Kyonghwa; Carson, Joshua; Gholami, Sepideh; Haddad, Dana; Gaujoux, Sebastien; Monette, Sebastien; Ezell, Paula; Wolchok, Jedd; Fong, Yuman.

In: Surgery (United States), Vol. 154, No. 3, 01.09.2013, p. 496-503.

Research output: Contribution to journalArticle

Au, JT, Mittra, A, Song, TJ, Cavnar, M, Jun, K, Carson, J, Gholami, S, Haddad, D, Gaujoux, S, Monette, S, Ezell, P, Wolchok, J & Fong, Y 2013, 'Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response', Surgery (United States), vol. 154, no. 3, pp. 496-503. https://doi.org/10.1016/j.surg.2013.06.005
Au, Joyce T. ; Mittra, Arjun ; Song, Tae Jin ; Cavnar, Michael ; Jun, Kyonghwa ; Carson, Joshua ; Gholami, Sepideh ; Haddad, Dana ; Gaujoux, Sebastien ; Monette, Sebastien ; Ezell, Paula ; Wolchok, Jedd ; Fong, Yuman. / Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response. In: Surgery (United States). 2013 ; Vol. 154, No. 3. pp. 496-503.
@article{a6bba25040324359b146e2b55d4156c4,
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.",
author = "Au, {Joyce T.} and Arjun Mittra and Song, {Tae Jin} and Michael Cavnar and Kyonghwa Jun and Joshua Carson and Sepideh Gholami and Dana Haddad and Sebastien Gaujoux and Sebastien Monette and Paula Ezell and Jedd Wolchok and Yuman Fong",
year = "2013",
month = "9",
day = "1",
doi = "10.1016/j.surg.2013.06.005",
language = "English (US)",
volume = "154",
pages = "496--503",
journal = "Surgery (United States)",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response

AU - Au, Joyce T.

AU - Mittra, Arjun

AU - Song, Tae Jin

AU - Cavnar, Michael

AU - Jun, Kyonghwa

AU - Carson, Joshua

AU - Gholami, Sepideh

AU - Haddad, Dana

AU - Gaujoux, Sebastien

AU - Monette, Sebastien

AU - Ezell, Paula

AU - Wolchok, Jedd

AU - Fong, Yuman

PY - 2013/9/1

Y1 - 2013/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84883228585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883228585&partnerID=8YFLogxK

U2 - 10.1016/j.surg.2013.06.005

DO - 10.1016/j.surg.2013.06.005

M3 - Article

VL - 154

SP - 496

EP - 503

JO - Surgery (United States)

JF - Surgery (United States)

SN - 0039-6060

IS - 3

ER -