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Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/59474

Title: Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo
Authors: Matsumoto, Misako Browse this author →KAKEN DB
Tatematsu, Megumi Browse this author
Nishikawa, Fumiko Browse this author
Azuma, Masahiro Browse this author
Ishii, Noriko Browse this author
Morii-Sakai, Akiko Browse this author
Shime, Hiroaki Browse this author →KAKEN DB
Seya, Tsukasa Browse this author →KAKEN DB
Issue Date: Feb-2015
Publisher: Nature Publishing Group
Journal Title: Nature Communications
Volume: 6
Start Page: 6280
Publisher DOI: 10.1038/ncomms7280
PMID: 25692975
Abstract: Ligand stimulation of the Toll-like receptors (TLRs) triggers innate immune response, cytokine production and cellular immune activation in dendritic cells. However, most TLR ligands are microbial constituents, which cause inflammation and toxicity. Toxic response could be reduced for secure immunotherapy through the use of chemically synthesized ligands with defined functions. Here we create an RNA ligand for TLR3 with no ability to activate the RIG-I/MDA5 pathway. This TLR3 ligand is a chimeric molecule consisting of phosphorothioate ODN-guided dsRNA (sODN-dsRNA), which elicits far less cytokine production than poly(I:C) in vitro and in vivo. The activation of TLR3/TICAM-1 pathway by sODN-dsRNA effectively induces natural killer and cytotoxic T cells in tumour-loaded mice, thereby establishing antitumour immunity. Systemic cytokinemia does not occur following subcutaneous or even intraperitoneal administration of sODN-dsRNA, indicating that TICAM-1 signalling with minute local cytokines sufficiently activate dendritic cells to prime tumoricidal effectors in vivo.
Rights: http://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/59474
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 瀬谷 司

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