Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas

Tevz, Gregor, Kranjc, Simona, Cemazar, Maja, Kamensek, Urska, Coer, Andrej, Krzan, Mojca, Vidic, Suzana, Pavlin, Darja, & Sersa, Gregor (2009) Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas. Journal of Gene Medicine, 11(12), pp. 1125-1137.

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Background: The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)-12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side-effects of IL-12 gene therapy, the objective was to achieve the controlled release of IL-12 after intramuscular gene electrotransfer. Methods: Gene electrotransfer of the plasmid pORF-mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL-12 was monitored in the serum of mice after carrying out two sets of intramuscular IL-12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL-12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X-rays, was evaluated on subcutaneous SA-1 and LPB tumors, as well as on lung metastases. Results: A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL-12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3-fold was determined. The amount of circulating IL-12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid. Conclusions: The present study demonstrates the feasibility of treatment by IL-12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.

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ID Code: 73290
Item Type: Journal Article
Refereed: Yes
Keywords: Gene electrotransfer, Interleukin-12, Irradiation, Mice, Sarcoma, interleukin 12, plasmid DNA, A J mouse, animal cell, animal experiment, animal model, animal tissue, antineoplastic activity, article, C57BL 6 mouse, cancer gene therapy, controlled drug release, controlled study, drug blood level, drug distribution, drug efficacy, electroporation, feasibility study, histopathology, ionizing radiation, lung metastasis, mouse, nonhuman, open reading frame, plasmid, priority journal, radiosensitization, Animals, Combined Modality Therapy, Female, Gene Therapy, Gene Transfer Techniques, Injections, Intramuscular, Lung Neoplasms, Mice, Inbred A, Mice, Inbred C57BL, Muscle, Skeletal, Radiation, Ionizing, Sarcoma, Experimental, Transfection, Murinae, Mus
DOI: 10.1002/jgm.1403
ISSN: 1099-498X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 08 Jul 2014 00:33
Last Modified: 08 Jul 2014 23:30

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