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Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]

Cancer Gene Therapy volume 11, pages 103–108 (2004)Cite this article

Abstract

Delivery of the interleukin-12 (IL-12) gene to solid tumors is a promising anticancer therapy. Vectors are currently being developed to achieve safe and effective intratumoral delivery of the IL-12 gene. Poly [D,L-2,4-diaminobutyric acid] (PDBA) is a novel gene carrier that was recently described. The goal of this study was to use this gene delivery system for treatment of solid tumors. To determine the optimal conditions for transfection, established B16F10-melanomas in C57BL/6 mice were treated with intratumoral injection of the PDBA/plasmid luciferase (pLuc) complex. We determined that the optimal complex composition was 50 μg/ml pLuc and 150 μg/ml PDBA. High levels of IL-12 protein were expressed in tumors after a single injection of PDBA/murine IL-12 (pmIL-12) complex, whereas serum levels of IL-12 in treated mice were below the limits of detection. IL-12 gene therapy with the PDBA system significantly inhibited tumor growth in comparison with the controls (P<.001). Moreover, both natural killer and cytotoxic T lymphocyte activities from draining lymph nodes of PDBA/pmIL-12-treated mice were increased substantially in comparison with those of controls (P<.05). These results suggest that PDBA-mediated IL-12 gene therapy is a potential strategy for treatment of patients with solid tumors.

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Acknowledgements

We thank Dr Jun-ichi Miyazaki (Department of Nutrition and Physiological Chemistry, Osaka University Medical School, Osaka, Japan) for the mIL-12 plasmid, Dr Yo-ichi Yamashita (Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan) for helpful advice regarding statistical analyses, and Michiyo Hisaka and Fusayo Kawamura for excellent technical support.

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Authors and Affiliations

  1. Department of Surgery I, Oita University, Faculty of Medicine, Oita, Japan

    Yukio Iwashita, Tadashi Ogawa, Shigeru Goto & Seigo Kitano

  2. Research and Development Division, Hisamitsu Pharmaceutical Co., Inc., Ibaraki, Japan

    Masaru Nakanishi & Takeshi Goto

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  1. Yukio Iwashita
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  2. Tadashi Ogawa
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  3. Shigeru Goto
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Correspondence to Shigeru Goto.

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Iwashita, Y., Ogawa, T., Goto, S. et al. Effective transfer of interleukin-12 gene to solid tumors using a novel gene delivery system, poly [D,L-2,4-diaminobutyric acid]. Cancer Gene Ther 11, 103–108 (2004). https://doi.org/10.1038/sj.cgt.7700669

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