Antitumour effects of a bispecific trivalent antibody in multicellular tumour spheroids.
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.
Walz
Annette
A
Department of Head and Neck Surgery, Ludwig-Maximilians-University, Marchioninistr. 15, D-81377 Munich, Germany.
Mack
Brigitte
B
Schmitt
Bärbel
B
Gires
Olivier
O
Wollenberg
Barbara
B
Zeidler
Reinhard
R
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
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule