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Quadroma


A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells (via CD3) and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction.

At an equivalent dose a trifunctional antibody is more potent (more than 1,000-fold) in eliminating tumor cells than conventional antibodies. These drugs evoke the removal of tumor cells by means of (i) antibody-dependent cell-mediated cytoxicity, a process also described for conventional antibodies and more importantly by (ii) polyclonal cytotoxic T cell responses with emphasis on CD8 T cells. These trifunctional antibodies also elicit individual anti-tumor immune responses in cancer patients treated with e.g. catumaxomab; i.e. autologous antibodies as well as CD4 and CD8 T cells directed against the tumor were detected. Furthermore, putative cancer stem cells from malignant ascites fluid were eliminated due to catumaxomab treatment.

Catumaxomab, was the first to be approved for clinical use (in 2009 for the treatment of malignant ascites in cancer patients).

Examples include catumaxomab (EpCAM / CD3),ertumaxomab (HER2/neu / CD3),FBTA05 (CD20 / CD3, proposed trade name Lymphomun) and TRBS07 (GD2 / CD3, proposed trade name Ektomab), drugs against various types of cancer.


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