Targeted microbeads for attraction and induction of specific innate immune response in the tumor microenvironment.
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.
Shahar
Ehud
E
Migal, Kiryat Shmona, Israel.
Gorodetsky
Raphael
R
Gaberman
Elena
E
Aizenshtein
Elina
E
Pitcovski
Jacob
J
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
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