title: Antitumour effects of a bispecific trivalent antibody in multicellular tumour spheroids.
abstract: BACKGROUND
  New adjuvant immunological therapies that selectively redirect effector cells towards tumour cells are currently under development. These strategies include the use of bispecific antibodies as promising tools for the elimination of disseminated tumour cells and micrometastases. At present, bispecific molecules have demonstrated their antitumour potential in investigations in vitro using monolayer cell cultures. However, their effectiveness in vivo is less clear and expressive in vitro tumour models are in high demand.
  
  
  METHODS
  Three-dimensional multicellular tumour spheroids (MTS) are of intermediate complexity between monolayer cell cultures and solid tumours in patients and therefore represent a particularly promising in vitro system.
  
  
  RESULTS
  We show, here, the antitumour potential of a bispecific antibody, BiUII, in three-dimensional multicellular tumour spheroids and furthermore demonstrate that BiUII triggers peripheral blood mononuclear cells to invade MTSs and elicit the production of TNFalpha, resulting in the efficient destruction of tumour cells.
  
  
  CONCLUSIONS
  These results demonstrate that bispecific antibodies are capable of activating immune effector cells, resulting in the elimination of three-dimensional structures of tumour cells. The therapeutic potential of these antibodies in the clinical setting merits further investigations.
authors.affiliation: Department of Head and Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, D-81377 Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Walz
authors.forename: Brigitte
authors.initials: B
authors.lastname: Mack
authors.forename: Bärbel
authors.initials: B
authors.lastname: Schmitt
authors.forename: Olivier
authors.initials: O
authors.lastname: Gires
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
authors.forename: Reinhard
authors.initials: R
authors.lastname: Zeidler
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule