title: Targeted microbeads for attraction and induction of specific innate immune response in the tumor microenvironment.
abstract: Antitumor activity of molecules and cells of the innate immune system has been reported. Here we propose a method for targeting preferred innate immune cells and magnifying their tumoricidal effect at the tumor microenvironment, by modular multiple-component complexes (termed TILTAN). As a model, micro-scale complexes were assembled carrying monoclonal anti-HER2 antibodies, lipopolysaccharide and/or mannose. The complexes showed high binding capacity to HER2-positive cancer cells in vitro, high induction of interleukin-1 RNA transcription by the activated monocytes and ability to mediate monocytes' attachment to HER2-positive cells. TILTAN treatment was found safe in in vivo testing and induced change in interleukin-1 RNA transcription in tumors xenografts. We thus present a new vision of targeting a desired innate immune response to the tumor microenvironment.
authors.affiliation: Migal, Kiryat Shmona, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Shahar
authors.forename: Raphael
authors.initials: R
authors.lastname: Gorodetsky
authors.forename: Elena
authors.initials: E
authors.lastname: Gaberman
authors.forename: Elina
authors.initials: E
authors.lastname: Aizenshtein
authors.forename: Jacob
authors.initials: J
authors.lastname: Pitcovski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy; D007375:Interleukin-1 / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008358:Mannose / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D018675:Toxicity Tests; D000068878:Trastuzumab; D059016:Tumor Microenvironment / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019496:Cancer Vaccines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008358:Mannose; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab