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TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model

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Abstract

Introduction

Transduction of the granulocyte-macrophage colony stimulating factor (GM-CSF) gene into mouse tumor cells abrogates their tumorigenicity in vivo. Our previous report demonstrated that gene transduction of GM-CSF with either TARC or RANTES chemokines suppressed in vivo tumor formation. In this paper, we examined whether the addition of either recombinant TARC or RANTES proteins to irradiated GM-CSF-transduced tumor vaccine cells enhanced antitumor immunity against established mouse tumor models to examine its future clinical application.

Materials and methods

Three million irradiated WEHI3B cells retrovirally transduced with murine GM-CSF cDNA in combination with either recombinant TARC or RANTES were subcutaneously inoculated into syngeneic WEHI3B-preestablished BALB/c mice.

Results

Vaccinations were well tolerated. Mice treated with GM-CSF-transduced cells and the chemokines demonstrated significantly longer survival than mice treated with GM-CSF-transduced cells alone. Splenocytes harvested from mice treated with the former vaccines produced higher levels of IL-4, IL-6, IFN-γ, and TNF-α, suggesting enhanced innate and adaptive immunity. Immunohistochemical analysis of tumor sections after vaccination revealed a more significant contribution of CD4+ and CD8+ T cells to tumor repression in the combined vaccine groups than controls.

Conclusions

TARC and RANTES enhance the immunological antitumor effect induced by GM-CSF in mouse WEHI3B tumor models and may be clinically useful.

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Abbreviations

GM-CSF:

Granulocyte-macrophage colony stimulating factor

TARC:

Thymus and activation-regulated chemokine

RANTES:

Regulated on activation, normal T-cell expressed and secreted

APCs:

Antigen-presenting cells

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Acknowledgments

We thank Dr. Shinji Okano and Dr. Yoshikazu Yonemitsu, Kyushu University, for their helpful advices. We also thank Ms. Michiyo Okada for excellent technical assistance. This work was supported by grants from the Ministry of Health, Labor, and Welfare and the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan

    Hiroyuki Inoue, Mutsunori Iga, Meng Xin, Saori Asahi, Takafumi Nakamura, Ryo Kurita, Masaharu Nakayama, Yukoh Nakazaki & Kenzaburo Tani

  2. Department of Advanced Cell and Molecular Therapy, Kyushu University Hospital, Kyushu University, Fukuoka, 812-8582, Japan

    Hiroyuki Inoue, Mutsunori Iga, Meng Xin, Saori Asahi, Takafumi Nakamura, Ryo Kurita, Masaharu Nakayama, Yukoh Nakazaki & Kenzaburo Tani

  3. Institute of Diseases of the Chest, Kyushu University, Fukuoka, 812-8582, Japan

    Hiroyuki Inoue, Koichi Takayama & Yoichi Nakanishi

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  1. Hiroyuki Inoue
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  2. Mutsunori Iga
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  3. Meng Xin
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  4. Saori Asahi
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  11. Kenzaburo Tani
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Correspondence to Kenzaburo Tani.

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Inoue, H., Iga, M., Xin, M. et al. TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model. Cancer Immunol Immunother 57, 1399–1411 (2008). https://doi.org/10.1007/s00262-008-0476-7

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  • DOI: https://doi.org/10.1007/s00262-008-0476-7

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