Abstract
Vaccination represents one the most effective methods of preventing disease. Because dendritic cells (DCs) are the most efficient antigen presenting cells, exploiting their plasticity is likely to yield improved therapeutic vaccines. Herein, we applied a novel DC-based vaccine (i.e., DC loaded with leukemia antigens that have been transfected with an IL-10 siRNA capable of coordinately activating DCs via TLR7/8) in a rat model of acute myeloid leukemia. Leukemic rats treated with this new vaccine had less leukemic cell mass in their bone marrows and less extramedullar dissemination of the leukemic disease examined postmortem compared with rats given the control vaccine. Collectively, the new strategy demonstrates the possible usefulness of dual siRNAs as an immunomodulatory drug with antileukemic properties.
MeSH terms
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology
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Bone Marrow / immunology
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Bone Marrow / pathology
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology*
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Cytotoxicity, Immunologic
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Dendritic Cells / immunology*
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Dendritic Cells / transplantation
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Disease Models, Animal
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Gene Expression Regulation, Leukemic*
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Genetic Engineering / methods
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Humans
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Immunotherapy / methods
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Interleukin-10 / agonists
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Interleukin-10 / genetics
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Interleukin-10 / immunology*
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Leukemia, Myeloid, Acute / genetics
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Leukemia, Myeloid, Acute / immunology
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Leukemia, Myeloid, Acute / mortality
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Leukemia, Myeloid, Acute / prevention & control*
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RNA, Small Interfering / genetics*
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RNA, Small Interfering / immunology
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Rats
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Survival Analysis
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Toll-Like Receptor 7 / genetics
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Toll-Like Receptor 7 / immunology
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Toll-Like Receptor 8 / genetics
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Toll-Like Receptor 8 / immunology
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Transfection
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Vaccination
Substances
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Antigens, Neoplasm
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Cancer Vaccines
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RNA, Small Interfering
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TLR7 protein, rat
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Toll-Like Receptor 7
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Toll-Like Receptor 8
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Interleukin-10