title: Induction of efficient antitumor immunity using dendritic cells activated by recombinant Sendai virus and its modulation by exogenous IFN-beta gene.
abstract: 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-beta (SeV-murine IFN-beta (mIFN-beta)/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-beta/DC), but not immature DC and LPS/DC, dramatically improved the survival of animals. Furthermore, SeV-mIFN-beta/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-beta, and SeV/DC, therefore, warrants further investigation as a promising alternative for cancer immunotherapy.
authors.affiliation: Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Shibata
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Onimaru
authors.forename: Shihoko
authors.initials: S
authors.lastname: Sata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagata-Takeshita
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Tsugumine
authors.initials: T
authors.lastname: Zhu
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Moroi
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000821:virology; D016026:Bone Marrow Transplantation / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation* / Q000821:virology; D005260:Female; D016899:Interferon-beta / Q000235:genetics* / Q000502:physiology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D014614:Vaccines, Synthetic; D016899:Interferon-beta