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 (September 2013) Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a local and systemic response. Surgery, 154 (3). pp. 496-503. ISSN 0039-6060

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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.

Item Type:	Paper
Subjects:	diseases & disorders > neoplasms diseases & disorders > cancer > drugs and therapies > Immunotherapy bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > plasmid
CSHL Authors:	Gholami, Sepideh
Communities:	CSHL labs > Gholami Lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	September 2013
Date Deposited:	05 Oct 2023 18:51
Last Modified:	05 Oct 2023 18:51
PMCID:	PMC4140181
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/41144

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