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Published on: October 24, 2016
Cancer electrogene therapy with interleukin-12
Maja Cemazar1, Tomaz Jarm, Gregor Sersa
1Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia. mcemazar@onko-i.si
Abstract:
Electrogene therapy combines administration of plasmid DNA into tissue followed by local application of electric pulses. In electrogene therapy with interleukin-12 (IL-12), different routes of administration, different doses of plasmid DNA and different protocols for delivery of electric pulses were evaluated in numerous preclinical studies. Antitumor effectiveness was tested in different types of primary tumors, distantly growing tumors and induced metastases. Intratumoral IL-12 electrogene therapy has been proved to be very effective in local tumor control, having also a systemic effect. Intramuscular and peritumoral IL-12 electrogene therapy had also a pronounced systemic effect and when combined with other treatment strategies resulted in tumor cures. Antitumor effectiveness of IL-12 electrogene therapy is due to the induction of adaptive immunity and innate resistance and anti-angiogenic action. Translation of preclinical studies into clinical trials in human and veterinary oncology has started with encouraging results that would hopefully lead to further investigation of this therapy, also in combination with other cancer treatment modalities.
Insights
Electrogene therapy using interleukin-12 (IL-12) DNA shows significant antitumor effects by stimulating immunity and inhibiting blood vessel growth. This promising cancer treatment is advancing into clinical trials for human and veterinary oncology.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Electrogene therapy involves delivering plasmid DNA and applying electric pulses to tissues.
- Interleukin-12 (IL-12) electrogene therapy has been extensively studied preclinically for cancer treatment.
Purpose of the Study:
- To evaluate the antitumor effectiveness of IL-12 electrogene therapy across various preclinical models.
- To understand the mechanisms underlying IL-12 electrogene therapy's efficacy.
- To assess the potential for clinical translation in oncology.
Main Methods:
- Preclinical studies involving different administration routes (intratumoral, intramuscular, peritumoral) and electric pulse protocols.
- Testing efficacy against primary tumors, distant tumors, and induced metastases.
- Investigating the induction of adaptive immunity, innate resistance, and anti-angiogenic actions.
Main Results:
- Intratumoral IL-12 electrogene therapy demonstrated high local tumor control with systemic effects.
- Intramuscular and peritumoral administration also showed significant systemic effects.
- Combination strategies with IL-12 electrogene therapy led to tumor cures in some models.
Conclusions:
- IL-12 electrogene therapy is a potent antitumor strategy with dual local and systemic effects.
- The therapy's effectiveness is mediated by immune system activation and anti-angiogenesis.
- Clinical trials in human and veterinary oncology are underway, showing encouraging results for further investigation.
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