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Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas

Abstract

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both immunocompetent and immunodeficient mice, indicating the involvement of the innate immune system in response to DNA. In conclusion, this study demonstrated that the observed antitumor effects are not due to a single factor, but to a combination of factors.

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Acknowledgements

The work in this study was supported by NIH 1 R21 CA106860 (LH), by the Slovene Research Agency P3-0003 and J3-4259 (MC and VT), and by a Bilateral scientific cooperation between Republic of Slovenia and United States of America BI-US/11-12-011.

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Correspondence to L Heller.

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Heller, L., Todorovic, V. & Cemazar, M. Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas. Cancer Gene Ther 20, 695–700 (2013). https://doi.org/10.1038/cgt.2013.71

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