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Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction

Gene Therapy volume 12, pages 129–139 (2005)Cite this article

Abstract

Although dendritic cell (DC)-based immunotherapy is considered a promising approach for cancer treatment, a large quantity of DC vaccine is required for effective sensitization/activation of immune cells because of the poor migratory ability of administered DCs into regional lymphoid tissue. In this study, we created a DC vaccine sufficiently transduced with CC chemokine receptor-7 gene (CCR7/DCs) by applying RGD fiber-mutant adenovirus vector (AdRGD), and investigated its immunological characteristics and therapeutic efficacy. CCR7/DCs acquired strong chemotactic activity for CC chemokine ligand-21 (CCL21) and exhibited an immunophenotype similar to mature DCs but not immature DCs with regard to major histocompatibility complex/costimulatory molecule-expression levels and allogenic T cell proliferation-stimulating ability, while maintaining inherent endocytotic activity. Importantly, CCR7/DCs injected intradermally into mice could accumulate in draining lymph nodes about 5.5-fold more efficiently than control AdRGD-applied DCs. Reflecting these properties of CCR7/DCs, DC vaccine genetically engineered to simultaneously express endogenous antigen and CCR7 could elicit more effective antigen-specific immune response in vivo using a lower dosage than DC vaccine transduced with antigen alone. Therefore, the application of CCR7/DCs having positive migratory ability to lymphoid tissues may contribute to reduction of efforts and costs associated with DC vaccine preparation by considerably reducing the DC vaccine dosage needed to achieve effective treatment by DC-based immunotherapy.

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Acknowledgements

We are grateful to KIRIN Brewery Co., Ltd (Tokyo, Japan) for providing recombinant murine GM-CSF, to Dr Clifford V Harding (Department of Pathology, Case Western Reserve University, Cleveland, OH, USA) for providing the CD8-OVA 1.3 cells, and to Dr Masaru Okabe (Genome Information Research Center, Osaka University, Suita, Japan) for providing the C57BL/6 TgN(act-EGFP)OsbC14-Y01-FM131 mice. This study was supported in part by the Research on Health Sciences Focusing on Drug Innovation from the Japan Health Sciences Foundation; by a Grant-in-Aid for Young Scientists (16790114) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by Senri Life Science Foundation; by the Science Research Promotion Fund of the Japan Private School Promotion Foundation; by grants from the Bioventure Development Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by grants from the Ministry of Health, Labour and Welfare in Japan.

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Authors and Affiliations

  1. Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, Japan

    N Okada, N Mori, R Koretomo, T Fujita & A Yamamoto

  2. Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

    Y Okada

  3. Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan

    T Nakayama & O Yoshie

  4. Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan

    H Mizuguchi

  5. National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan

    T Hayakawa

  6. Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

    S Nakagawa & T Mayumi

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Okada, N., Mori, N., Koretomo, R. et al. Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction. Gene Ther 12, 129–139 (2005). https://doi.org/10.1038/sj.gt.3302358

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  • DOI: https://doi.org/10.1038/sj.gt.3302358

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