RRC ID 19312
Author Komaru A, Ueda Y, Furuya A, Tanaka S, Yoshida K, Kato T, Kinoh H, Harada Y, Suzuki H, Inoue M, Hasegawa M, Ichikawa T, Yonemitsu Y.
Title Sustained and NK/CD4+ T cell-dependent efficient prevention of lung metastasis induced by dendritic cells harboring recombinant Sendai virus.
Journal J Immunol
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.
Volume 183(7)
Pages 4211-9
Published 2009-10-1
DOI 10.4049/jimmunol.0803845
PII jimmunol.0803845
PMID 19734206
MeSH Animals CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / pathology* Cell Proliferation Cytotoxicity, Immunologic / genetics Dendritic Cells / immunology* Dendritic Cells / virology Killer Cells, Natural / immunology* Killer Cells, Natural / pathology* Lung Neoplasms / pathology Lung Neoplasms / prevention & control* Lung Neoplasms / secondary* Lymph Nodes / immunology Lymph Nodes / pathology Male Mice Mice, Inbred A Mice, Inbred BALB C Mice, Inbred C57BL Mice, Nude Mice, Transgenic Neuroblastoma / immunology Oncolytic Virotherapy Prostatic Neoplasms / immunology Prostatic Neoplasms / virology Sendai virus / genetics Sendai virus / immunology* Time Factors Vaccines, Synthetic / genetics Vaccines, Synthetic / immunology
IF 4.886
Times Cited 29
Human and Animal Cells C-1300(RCB0283)