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Updated: Aug 7, 2026
Electrochemotherapy of Tumours
Published on: December 15, 2008
Effective tumor therapy with plasmid-encoded cytokines combined with in vivo electroporation
1Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Abstract:
Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or IL-12 gene transduction on the growth of experimental murine tumors. Significant intratumoral gene transduction was achieved by electroporation of tumors that had been injected with naked plasmids encoding reporter genes and cytokine genes (IL-2 and IL-12) under the control of a constitutive cytomegalovirus promoter. In addition, significant tumor growth delay could be achieved in a murine melanoma line B16.F10 with the cytokine genes. Most importantly, systemic transgene levels were negligible when compared with intratumoral adenovirus-mediated IL-12 gene delivery, which leads to significantly higher systemic cytokine levels. Therefore, naked plasmid- and in vivo electroporation-mediated cancer gene therapy may be therapeutically efficacious while maintaining low systemic toxicity.
Insights
Electroporation with naked plasmids effectively delivers cytokine genes into tumors, significantly delaying tumor growth. This naked plasmid and in vivo electroporation gene therapy offers therapeutic benefits with low systemic toxicity.
Area of Science:
- Oncology
- Gene Therapy
- Immunology
Background:
- Plasmids offer advantages for gene delivery but face challenges with low in vivo transduction efficiency.
- Effective gene delivery is crucial for developing successful cancer gene therapies.
Purpose of the Study:
- To investigate the efficacy of electroporation-based gene transduction using naked plasmids encoding interleukin-2 (IL-2) or interleukin-12 (IL-12) for experimental murine tumor growth.
- To compare the systemic transgene levels of plasmid-based delivery with adenovirus-mediated delivery.
Main Methods:
- Utilized an electroporation-based approach for gene transduction in experimental murine tumors.
- Administered naked plasmids encoding reporter and cytokine genes (IL-2, IL-12) under a cytomegalovirus promoter.
- Evaluated tumor growth delay in the B16.F10 murine melanoma model.
Main Results:
- Achieved significant intratumoral gene transduction via electroporation of naked plasmid-injected tumors.
- Demonstrated significant tumor growth delay in the B16.F10 melanoma model following IL-2 or IL-12 gene transduction.
- Observed negligible systemic transgene levels compared to adenovirus-mediated IL-12 delivery, which resulted in higher systemic cytokine levels.
Conclusions:
- Naked plasmid and in vivo electroporation-mediated cancer gene therapy can achieve therapeutic efficacy.
- This approach shows potential for effective cancer treatment with reduced systemic toxicity.
- Intratumoral gene delivery via electroporation offers a promising strategy for localized cancer therapy.
