title: Flt3 ligand enhances anti-tumor effects of antibody therapeutics.
abstract: Fms-like tyrosine kinase 3 ligand ([Flt3 ligand], FL) stimulates proliferation and development of a wide range of hematopoietic cells including hematopoietic stem cells and myeloid and lymphoid progenitor cells. FL also has been shown to have anti-tumor effects in a variety of in vivo tumor models. In this study, the effect of FL against tumor growth was investigated in the COLO-205 human colon tumor xenograft model. FL was delivered in vivo by the "hydrodynamics-based gene delivery of naked DNA" method. In this experimental setting, FL and/or the therapeutic antibody anti-carcinoembryonic antigen (CEA) monoclonal antibody was administered. FL alone or anti-CEA antibody alone induced significant growth inhibition; furthermore, FL plus antibody treatment produced synergistic anti-tumor effects. This study is the first demonstration of a synergistic anti-tumor effect between FL and antibody therapeutics.
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Sunto-gun, Nagaizumi-cho, Shizuoka 411-8777, Japan. k.maruyama@scchr.jp
authors.forename: Kouji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Zohair
authors.initials: Z
authors.lastname: Selmani
authors.forename: Hidee
authors.initials: H
authors.lastname: Ishii
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tai
authors.forename: Jinyan
authors.initials: J
authors.lastname: Cheng
authors.forename: Shingo
authors.initials: S
authors.lastname: Akimoto
authors.forename: Morihiro
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D010957:Plasmids / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D018076:DNA, Complementary; D008565:Membrane Proteins; C084881:flt3 ligand protein