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. Materials and 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 TNFα, resulting in the efficient destruction of tumour cells. Conclusion: 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.