Medical Oncology

, 26:429 | Cite as

Induction of antigen-specific cytotoxic T lymphocytes by using monocyte-derived DCs transfected with in vitro-transcribed WT1 or SART1 mRNA

  • Miwako Narita
  • Nozomi Tochiki
  • Anri Saitoh
  • Norihiro Watanabe
  • Masami Kaji
  • Noriyuki Satoh
  • Akie Yamahira
  • Takeshi Nakamura
  • Masayoshi Masuko
  • Tatsuo Furukawa
  • Ken Toba
  • Ichiro Fuse
  • Yoshifusa Aizawa
  • Masuhiro Takahashi
Original Paper
First Online:
Received:
Accepted:

Abstract

To evaluate the usefulness of monocyte-derived dendritic cells transfected with tumor antigen mRNA for dendritic cell-based antitumor immunotherapy, we attempted to generate antigen-specific cytotoxic T cells by priming lymphocytes with monocyte-derived dendritic cells transfected with in vitro-transcribed tumor antigen mRNA. Mature monocyte-derived dendritic cells were generated from microbeads-separated CD14+ cells by culturing with GM-CSF/IL-4 for 7 days and with TNF-α, IL-1α, IL-6, and PGE2 for the last one day. Monocyte-derived dendritic cells, lymphocytes, and target cells, which were positive for HLA-A24, were used in the present study. Although lymphocytes prestimulated with untransfected monocyte-derived dendritic cells did not possess the cytotoxic ability against the target cells in a 51Cr-release cytotoxicity assay, lymphocytes primed with tumor antigen RNA-transfected monocyte-derived dendritic cells were cytotoxic against the tumor antigen-expressing cells but not against the target cells without the expression of the antigen. The cytotoxic ability of the lymphocytes was blocked by the addition of antibodies against MHC class I but not by antibodies against MHC class II. These findings revealed that monocyte-derived dendritic cells transfected with WT1 or SART1 mRNA are able to induce tumor antigen-specific cytotoxic T cells and applicable for antitumor dendritic cell-based cellular immunotherapy.

Keywords

Antigen-specific CTL Monocyte-derived DCs WT1 SART1 In vitro-transcribed mRNA Transfection Cytotoxicity MHC class I restriction Antitumor cellular immunotherapy 
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Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  • Miwako Narita
    • 1
  • Nozomi Tochiki
    • 1
  • Anri Saitoh
    • 1
  • Norihiro Watanabe
    • 1
  • Masami Kaji
    • 1
  • Noriyuki Satoh
    • 1
  • Akie Yamahira
    • 1
  • Takeshi Nakamura
    • 1
  • Masayoshi Masuko
    • 2
  • Tatsuo Furukawa
    • 2
  • Ken Toba
    • 3
  • Ichiro Fuse
    • 4
  • Yoshifusa Aizawa
    • 3
  • Masuhiro Takahashi
    • 1
  1. 1.Laboratory of Hematology and Oncology, Graduate School of Health SciencesNiigata UniversityNiigataJapan
  2. 2.Division of Stem Cell TransplantationNiigata University Medical and Dental General HospitalNiigataJapan
  3. 3.Division of Hematology, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
  4. 4.Division of Bioscience Medical Research CenterNiigata University Medical and Dental General HospitalNiigataJapan

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