Trifunctional antibody
Monoclonal antibody / From Wikipedia, the free encyclopedia
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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.[1]
At an equivalent dose a trifunctional antibody is more potent (more than 1,000-fold) in eliminating tumor cells than conventional antibodies.[2] 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.[3][4] Furthermore, putative cancer stem cells from malignant ascites fluid were eliminated due to catumaxomab treatment.[5]
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),[6][7] ertumaxomab (HER2/neu / CD3),[8] FBTA05 (CD20 / CD3, proposed trade name Lymphomun)[9][10] and TRBS07 (GD2 / CD3, proposed trade name Ektomab),[11] drugs against various types of cancer.