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Combined IL-12 and GM-CSF gene therapy for murine hepatocellular carcinoma

Cancer Gene Therapy volume 8, pages 751–758 (2001)Cite this article

Abstract

Among various immunotherapeutic approaches, interleukin-12 (IL-12) is particularly appealing because of its superior antitumor effects, which have been demonstrated in preclinical as well as clinical studies. However, IL-12 therapy was often accompanied by severe side effects due mainly to the supranormal induction of interferon-γ. To optimize the therapeutic efficacy and lower the side effects of IL-12, we have investigated the antitumor activity of combined IL-12 and granulocyte–macrophage colony-stimulating factor (GM-CSF) gene therapy in a highly malignant and poorly immunogenic murine hepatocellular carcinoma model. Using a versatile hydrodynamics-based DNA delivery method, we showed that the combined gene delivery of IL-12 and GM-CSF induced very strong antitumor cellular immunity and achieved significant therapeutic efficacy, whereas each cytokine gene alone yielded appreciable but less effects. We also observed that the combined therapy induced lower levels of interferon-γ than did IL-12 alone. These results suggest that combined IL-12 and GM-CSF therapy can render a stronger antitumor effect as well as lowering potential side effects. Cancer Gene Therapy (2001) 8, 751–758

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Acknowledgements

The authors thank Michael Y. Xiao for critical reading and editing of English. This work is supported, in part, by a grant from the State Key Basic Research Program in China (G1998051211).

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  1. Zhong Wang and Shuang-Jian Qiu: These two authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, 15261, Pennsylvania, USA

    Zhong Wang & Xiao Xiao

  2. Liver Cancer Institute, Zhong Shan Hospital, Fudan University Medical Center, Shanghai, China

    Shuang-Jian Qiu, Sheng-Long Ye & Zhao-You Tang

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  1. Zhong Wang
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  2. Shuang-Jian Qiu
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Correspondence to Xiao Xiao.

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Wang, Z., Qiu, SJ., Ye, SL. et al. Combined IL-12 and GM-CSF gene therapy for murine hepatocellular carcinoma. Cancer Gene Ther 8, 751–758 (2001). https://doi.org/10.1038/sj.cgt.7700375

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  • DOI: https://doi.org/10.1038/sj.cgt.7700375

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