Anti-tumor effect of in vivo IL-2 and GM-CSF electrogene therapy in murine hepatoma model
Journal
Anticancer Research
Journal Volume
23
Journal Issue
1 A
Pages
315-321
Date Issued
2003
Author(s)
Abstract
Background: We evaluated the effect of in vivo electrogene therapy (EGT), a newly-developed gene transfer method using electroporation on the induction of anti-cancer immunity. Materials and Methods: The in vivo EGT was carried out by direct injection of plasmid DNAs encoding mouse interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a subcutaneous murine hepatoma model of 1MEA.7R.1 cells. Six electric pulses were generated in situ from a square-wave electroporator fitted with a circular, six-needle electrode array. 1MEA.7R.1 cells in vitro were modified to secret IL-2 (1MEA.7R.1/IL-2 cells). Results: The 1MEA.7R.1/IL-2 cells had a similar cell doubling-time as their parent cells but showed a much slower growth rate on Balb/C mice. One, or 3 rounds of single gene EGT with IL-2 gene showed a dose-responsive effect of growth retardation. Coadministration of 3 rounds of IL-2/GM-CSF double genes EGT had a stronger growth inhibition effect than 3 rounds of IL-2 single gene EGT. Three rounds of IL-2/GM-CSF EGT rendered the tumor to a growth rate of stably transfected 1MEA.7R.1/IL-2 cells. Seven rounds of IL-2/GM-CSF EGT markedly inhibited the tumor growth. Reverse transciptase-polymerase chain reaction confirmed the expression of IL-2, GM-CSF and interferon-gamma within treated tumors. Systemic inhibitory effects can be demonstrated from tumor-re-challenged experiments on mice which received 3 rounds of double-gene EGT. The T cell proliferation assay revealed an increased T cell proliferation in double-gene EGT-treated mice. Conclusion: This experiment showed that partial systemic immunity can be provoked by IL-2/GM-CSF double-gene EGT. These findings suggest that our immuno-gene therapy protocol has the potential for future clinical applications.
Subjects
Electrogene therapy; Electroporation; Gene therapy; GM-CSF; IL-2
SDGs
Other Subjects
gamma interferon; granulocyte macrophage colony stimulating factor; interleukin 2; plasmid DNA; animal cell; animal experiment; animal model; antineoplastic activity; article; cancer immunotherapy; cancer inhibition; cellular immunity; controlled study; dose response; electrogene therapy; electroporation; gene therapy; gene transfer; liver cell carcinoma; lymphocyte proliferation; mouse; nonhuman; priority journal; reverse transcription polymerase chain reaction; T lymphocyte; Animals; Electroporation; Gene Therapy; Granulocyte-Macrophage Colony-Stimulating Factor; Interleukin-2; Liver Neoplasms, Experimental; Mice; Mice, Inbred BALB C; RNA, Messenger
Type
journal article