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

Authors
  • Narita, Miwako1
  • Tochiki, Nozomi
  • Saitoh, Anri
  • Watanabe, Norihiro
  • Kaji, Masami
  • Satoh, Noriyuki
  • Yamahira, Akie
  • Nakamura, Takeshi
  • Masuko, Masayoshi
  • Furukawa, Tatsuo
  • Toba, Ken
  • Fuse, Ichiro
  • Aizawa, Yoshifusa
  • Takahashi, Masuhiro
  • 1 Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, 2-746, Asahimachi-dori, Niigata 951-8518, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Medical Oncology
Publisher
Springer-Verlag
Publication Date
Dec 01, 2009
Volume
26
Issue
4
Pages
429–436
Identifiers
DOI: 10.1007/s12032-008-9142-3
PMID: 19058036
Source
Medline
License
Unknown

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-alpha, IL-1alpha, IL-6, and PGE(2) 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 (51)Cr-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.

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