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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2008

01-09-2008 | Original Article

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

Authors: Hiroyuki Inoue, Mutsunori Iga, Meng Xin, Saori Asahi, Takafumi Nakamura, Ryo Kurita, Masaharu Nakayama, Yukoh Nakazaki, Koichi Takayama, Yoichi Nakanishi, Kenzaburo Tani

Published in: Cancer Immunology, Immunotherapy | Issue 9/2008

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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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Metadata
Title
TARC and RANTES enhance antitumor immunity induced by the GM-CSF-transduced tumor vaccine in a mouse tumor model
Authors
Hiroyuki Inoue
Mutsunori Iga
Meng Xin
Saori Asahi
Takafumi Nakamura
Ryo Kurita
Masaharu Nakayama
Yukoh Nakazaki
Koichi Takayama
Yoichi Nakanishi
Kenzaburo Tani
Publication date
01-09-2008
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 9/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0476-7

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