| RIG-I helicase-independent pathway in sendai virus-activated dendritic cells is critical for preventing lung metastasis of AT6.3 prostate cancer. | |
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MedLine Citation:
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PMID: 21076616 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs) activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV), and proposed a new concept, "immunostimulatory virotherapy," for cancer immunotherapy. However, there has been little information on the efficacies of this method: 1) in more clinically relevant situations including metastatic diseases, 2) on other tumor types and other animal species, and 3) on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP)-activated bone marrow-derived DCs (rSeV/dF-GFP-DC), consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I) (rSeV/dF-RIGIC-DC), an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies. |
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Authors:
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Tomonori Kato; Yasuji Ueda; Hiroaki Kinoh; Yasuo Yoneyama; Akinao Matsunaga; Atsushi Komaru; Yui Harada; Hiroyoshi Suzuki; Akira Komiya; Satoko Shibata; Mamoru Hasegawa; Hideki Hayashi; Tomohiko Ichikawa; Yoshikazu Yonemitsu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Neoplasia (New York, N.Y.) Volume: 12 ISSN: 1476-5586 ISO Abbreviation: Neoplasia Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100886622 Medline TA: Neoplasia Country: Canada |
Other Details:
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Languages: eng Pagination: 906-14 Citation Subset: IM |
Affiliation:
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Department of Gene Therapy, Chiba University Graduate School of Medicine, Chiba, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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