title: Sustained and NK/CD4+ T cell-dependent efficient prevention of lung metastasis induced by dendritic cells harboring recombinant Sendai virus.
abstract: We recently demonstrated efficient antitumor immunity against murine tumors using dendritic cells (DCs) activated by recombinant Sendai viruses (rSeVs), and proposed a new concept, "immunostimulatory virotherapy," for cancer immunotherapy. However, there has been little information on the efficacy of this method in preventing metastatic diseases. In this study, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV (rSeV/dF) using a murine model of lung metastasis. Bolus and i.v. administration of DCs harboring rSeV/dF-expressing GFP without pulsation of tumor Ag (DC-rSeV/dF-GFP) 2 days before tumor inoculation showed efficient prevention against lung metastasis of c1300 neuroblastoma, but not of RM-9 prostatic cancer. We found that the timing of DC therapy was critical for the inhibition of pulmonary metastasis of RM-9, and that the optimal effect of DCs was seen 28 days before tumor inoculation. Interestingly, the antimetastatic effect was sustained for over 3 mo, even when administered DCs were already cleared from the lung and organs related to the immune system. Although NK cell activity had already declined to baseline at the time of tumor inoculation, Ab-mediated depletion studies revealed that CD4+ cells as well as the presence of, but not the activation of, NK cells were crucial to the prevention of lung metastasis. These results are the first demonstration of efficient inhibition of lung metastasis via bolus administration of virally activated DCs that was sustained and NK/CD4+ cell-dependent, and may suggest a potentially new mechanism of DC-based immunotherapy for advanced malignancies.
authors.affiliation: Department of Gene Therapy, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Komaru
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Ueda
authors.forename: Aki
authors.initials: A
authors.lastname: Furuya
authors.forename: Sakura
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kumi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kinoh
authors.forename: Yui
authors.initials: Y
authors.lastname: Harada
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D009447:Neuroblastoma / Q000276:immunology; D050130:Oncolytic Virotherapy; D011471:Prostatic Neoplasms / Q000276:immunology / Q000821:virology; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D013997:Time Factors; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D014614:Vaccines, Synthetic