title: Engineering therapeutic cancer vaccines that activate antitumor immunity.
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.
authors.affiliation: Department of Nutrition, Oslo University Hospital, Norway, Montebello, 0310, Norway.
authors.forename: Per Ole
authors.initials: PO
authors.lastname: Iversen
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004195:Disease Models, Animal; D015973:Gene Expression Regulation, Leukemic; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000819:agonists / Q000235:genetics / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000276:immunology; D051381:Rats; D016019:Survival Analysis; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014611:Vaccination
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D034741:RNA, Small Interfering; C489639:TLR7 protein, rat; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D016753:Interleukin-10