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Gene1
* Division of Pathophysiological and Experimental Pathology, Department of Pathology and
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and
DNAVEC Corporation, Tsukuba, Ibaraki, Japan
Dendritic cell (DC)-based cancer immunotherapy has been paid much attention as a new and cancer cell-specific therapeutic in the last decade; however, little clinical outcome has been reported. Current limitations of DC-based cancer immunotherapy include sparse information about which DC phenotype should be administered. We here report a unique, representative, and powerful method to activate DCs, namely recombinant Sendai virus-modified DCs (SeV/DC), for cancer immunotherapy. In vitro treatment of SeV without any bioactive gene solely led DCs to a mature phenotype. Even though the expression of surface markers for DC activation ex vivo did not always reach the level attained by an optimized amount of LPS, superior antitumor effects to B16F1 melanoma, namely tumor elimination and survival, were obtained with use of SeV-GFP/DC as compared with those seen with LPS/DC in vivo, and the effect was enhanced by SeV/DC-expressing IFN-
(SeV-murine IFN- (mIFN-)/DC). In case of the treatment of an established tumor of B16F10 (7–9 mm in diameter), a highly malignant subline of B16 melanoma, SeV-modified DCs (both SeV-GFP/DC and SeV-mIFN-/DC), but not immature DC and LPS/DC, dramatically improved the survival of animals. Furthermore, SeV-mIFN-/DC but not other DCs could lead B16F10 tumor to the dormancy, associated with strongly enhanced CD8+ CTL responses. These results indicate that rSeV is a new and powerful tool as an immune booster for DC-based cancer immunotherapy that can be significantly modified by IFN-, and SeV/DC, therefore, warrants further investigation as a promising alternative for cancer immunotherapy.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by a Grant-in-Aid (to Y.Y. and K.S.) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology; and by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (to Y.Y. and K.S.; Project MF-21).
2 Address correspondence and reprint requests to Dr. Yoshikazu Yonemitsu, Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail address: yonemitu{at}med.kyushu-u.ac.jp
3 Abbreviations used in this paper: DC, dendritic cell; SeV, recombinant Sendai virus; SeV/DC, SeV-modified DC; mIFN-, murine IFN-; mBM-DC, bone marrow-derived DC; i.t., intratumoral; T-reg, regulatory T; MOI, multiplicity of infection; LCMV, lymphocytic choriomeningitis virus; fsc/ssc, forward scatter/side scatter.
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