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Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects

Cancer Gene Therapy volume 10, pages 771–778 (2003)Cite this article

Abstract

We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected into nude or severe combined immunodeficiency (SCID) mice. Although the proliferation in vitro of the transduced cells remained the same as that of parent cells, growth of AsPC-1/IL-21 and AsPC-1/IL-23 tumors developed in nude mice was retarded compared with that of parent tumors. Treatment of nude mice with anti-asialo GM1 antibody temporally abrogated the growth retardation of AsPC-1/IL-21, but not AsPC-1/IL-23 tumors; however, the growth of AsPC-1/IL-21 tumors came to be retarded thereafter with the regeneration of natural killer (NK) cells. The growth of AsPC-1/IL-21 tumors developed in SCID mice was also retarded compared with parent tumors and the growth retardation was abrogated by treatment with anti-asialo GM1 antibody. The growth of AsPC-1/IL-23 tumors in SCID mice was not different from that of parent tumors. Cytotoxic activity and secretion of interferon-γ in response to AsPC-1 cells were induced in spleen cells of the mice bearing AsPC-1/IL-21 or AsPC-1/IL-23 tumors. When nude mice were injected with a mixed population of AsPC-1/IL-21 and AsPC-1/IL-23 cells, no synergistic effects were observed. These data collectively suggest that expression of IL-21 and IL-23 in tumors can produce NK cell-dependent and -independent antitumor effects in an αβ T cell-defective condition, respectively.

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Acknowledgements

This work was supported by a grants-in-aid for scientific research from the Japan Society for the Promotion of Science (JSPS) and the Uehara Memorial Foundation. Ling Yu and Yan-Qing Wang were supported by the JSPS postdoctoral fellowship.

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Authors and Affiliations

  1. Division of Pathology, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, 260-8717, Chiba, Japan

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

  2. Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, 260-8670, Chiba, Japan

    Shin-ichi Ugai, Taketo Yamaguchi & Hiromitsu Saisho

  3. Department of Neurobiology, State Key Laboratory of Medical Neurobiology, Medical Center of Fudan University, Shanghai, 200032, China

    Yan-Qing Wang

  4. Department of Immunology, Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hiroshi Yamamoto

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  1. Shin-ichi Ugai
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  2. Osamu Shimozato
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  10. Masatoshi Tagawa
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Correspondence to Masatoshi Tagawa.

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Ugai, Si., Shimozato, O., Yu, L. et al. Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and -independent antitumor effects. Cancer Gene Ther 10, 771–778 (2003). https://doi.org/10.1038/sj.cgt.7700630

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  • DOI: https://doi.org/10.1038/sj.cgt.7700630

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