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Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts

Cancer Gene Therapy volume 10, pages 187–192 (2003)Cite this article

Abstract

Interleukin-21 (IL-21) is a novel cytokine that can induce proliferation of activated T cells and maturation of natural killer (NK) cells. We therefore examined whether expression of the IL-21 gene in tumor cells could generate antitumor responses. Murine colon carcinoma Colon 26 cells that were transduced with the mouse IL-21 gene (Colon 26/IL-21) were rejected in syngeneic mice and the mice subsequently acquired protective immunity. The growth of Colon 26/IL-21 tumors developed in nude mice was retarded compared with that of parent tumors, and this growth suppression was not observed in nude mice that were treated with anti-asialo GM1 antibody. Spleen cells from the mice that had rejected Colon 26/IL-21 cells showed cytotoxic activity to Colon 26 but not to irrelevant tumor cells, and produced larger amounts of interferon-γ upon stimulation with irradiated Colon 26 cells. Spleen cells from Colon 26/IL-21-tumor- but not parent-tumor-bearing mice had lytic activity to YAC-1 cells. These data suggest that expression of IL-21 in tumors induces T- and NK-cell-dependent antitumor effects.

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Acknowledgements

This work was supported by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (JSPS) and the Uehara Memorial Foundation. Y-Q Wang was supported by a JSPS fellowship.

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Authors and Affiliations

  1. Department of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan

    Shin-ichi Ugai, Osamu Shimozato, Kiyoko Kawamura, Yan-Qing Wang, Shigeru Sakiyama & Masatoshi Tagawa

  2. Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Shin-ichi Ugai, Taketo Yamaguchi & Hiromitsu Saisho

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  1. Shin-ichi Ugai
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  2. Osamu Shimozato
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  3. Kiyoko Kawamura
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  6. Hiromitsu Saisho
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  7. Shigeru Sakiyama
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  8. Masatoshi Tagawa
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Correspondence to Masatoshi Tagawa.

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Ugai, Si., Shimozato, O., Kawamura, K. et al. Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts. Cancer Gene Ther 10, 187–192 (2003). https://doi.org/10.1038/sj.cgt.7700552

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