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
Data(s) |
2009
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Resumo |
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. |
Identificador | |
Publicador |
John Wiley & Sons, Inc. |
Relação |
DOI:10.1002/jgm.1403 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. |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #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 |
Tipo |
Journal Article |