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

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

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1399-1411
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume57
Issue number9
DOIs
Publication statusPublished - Sep 1 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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