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[Cancer Research 61, 3281-3284, April 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Effective Tumor Therapy with Plasmid-encoded Cytokines Combined with in Vivo Electroporation1

Frank Lohr2, David Y. Lo, David A. Zaharoff, Kang Hu, Xiuwu Zhang, Yongping Li, Yulin Zhao, Mark W. Dewhirst, Fan Yuan and Chuan-Yuan Li3

Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 [F. L., D. Y. L., K. H., X. Z., Y. L., Y. Z., M. W. D., C-Y. L.], and Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 [D. A. Z., F. Y.]

Plasmids may have unique advantages as a gene delivery system. However, a major obstacle is the low in vivo transduction efficiency. In this study, an electroporation-based gene transduction approach was taken to study the effect of interleukin (IL)-2 or IL-12 gene transduction on the growth of experimental murine tumors. Significant intratumoral gene transduction was achieved by electroporation of tumors that had been injected with naked plasmids encoding reporter genes and cytokine genes (IL-2 and IL-12) under the control of a constitutive cytomegalovirus promoter. In addition, significant tumor growth delay could be achieved in a murine melanoma line B16.F10 with the cytokine genes. Most importantly, systemic transgene levels were negligible when compared with intratumoral adenovirus-mediated IL-12 gene delivery, which leads to significantly higher systemic cytokine levels. Therefore, naked plasmid- and in vivo electroporation-mediated cancer gene therapy may be therapeutically efficacious while maintaining low systemic toxicity.




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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2001 by the American Association for Cancer Research.