RRC ID 43194
Author Kitajima M, Abe T, Miyano-Kurosaki N, Taniguchi M, Nakayama T, Takaku H.
Title Induction of natural killer cell-dependent antitumor immunity by the Autographa californica multiple nuclear polyhedrosis virus.
Journal Mol Ther
Abstract Wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a variety of mammalian cell types in vitro, but does not replicate in these cells. We investigated the effects of AcMNPV in the induction of the immune response and tumor metastasis in mice. After intravenous injection, AcMNPV was taken up by the liver and spleen, and preferentially infected dendritic cells (DCs) and B cells in the spleen; costimulatory molecules CD40, CD80, and CD86 were upregulated in the DCs. The hepatic mononuclear cells (MNCs) in these animals were highly cytotoxic to natural killer (NK)-sensitive YAC-1 and B16 melanoma cells, but not to NK-resistant EL4 cells. Intravenous injection of AcMNPV-induced NK cell proliferation in the liver and spleen, and enhanced antitumor immunity in mice with B16 liver metastases. Furthermore, such treatment increased the survival of C57BL/6, J alpha 281 (-/-), and interferon (IFN)-gamma (-/-) mice that were previously injected with B16 tumor cells. AcMNPV injection did not enhance the survival of NK cell-depleted mice. Moreover, one AcMNPV treatment effectively prolonged survival in a B16 liver metastasis model, and was equivalent to five treatments with recombinant interleukin-12 (IL-12) protein. These findings suggest that AcMNPV efficiently stimulates NK cell-mediated antitumor immunity.
Volume 16(2)
Pages 261-8
Published 2008-2-1
DOI 10.1038/sj.mt.6300364
PII S1525-0016(16)31391-0
PMID 18059370
MeSH Alanine Transaminase / blood Animals Aspartate Aminotransferases / blood B7-1 Antigen / immunology B7-2 Antigen / immunology CD40 Antigens / immunology Cell Line, Tumor Cytotoxicity, Immunologic / immunology Female Flow Cytometry Immunity / immunology* Immunotherapy / methods Interferon-gamma / genetics Interferon-gamma / immunology Interleukin-12 / genetics Interleukin-12 / immunology Killer Cells, Natural / immunology* Liver Neoplasms / immunology Liver Neoplasms / secondary Melanoma, Experimental / immunology Melanoma, Experimental / pathology Melanoma, Experimental / therapy Mice Mice, Inbred C57BL Mice, Knockout Neoplasms, Experimental / immunology* Neoplasms, Experimental / pathology Neoplasms, Experimental / therapy Nucleopolyhedroviruses / genetics Nucleopolyhedroviruses / immunology* Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Spleen / immunology Spleen / pathology
IF 8.402
Times Cited 37
Human and Animal Cells