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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
Author(s) -
Tevz Gregor,
Kranjc Simona,
Cemazar Maja,
Kamensek Urska,
Coer Andrej,
Krzan Mojca,
Vidic Suzana,
Pavlin Darja,
Sersa Gregor
Publication year - 2009
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1403
Subject(s) - genetic enhancement , cancer research , gene , lung cancer , biology , medicine , pathology , biochemistry
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.