Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy.
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Seimetz D, Lindhofer H, Bokemeyer C
Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy.
Cancer Treat Rev. 2010 Oct;36(6):458-67. doi: 10.1016/j.ctrv.2010.03.001. Epub 2010 Mar 27.
- PubMed ID
- 20347527 [ View in PubMed]
- Abstract
Catumaxomab is a trifunctional antibody (trAb) characterized by its unique ability to bind three different cell types: tumor cells, T-cells, and accessory cells. It has two different antigen-binding specificities: one for epithelial cell adhesion molecule (EpCAM) on tumor cells and one for the CD3 antigen on T-cells. Catumaxomab also binds to type I, IIa, and III Fcgamma receptors (FcgammaR) on accessory cells, e.g. macrophages, dendritic cells, and natural killer cells, via its intact Fc region. Its anti-tumor activity results from T-cell-mediated lysis, antibody-dependent cell-mediated cytotoxicity, and phagocytosis via activation of FcgammaR-positive accessory cells. Importantly, no additional activation of immune cells is necessary for effective tumor eradication by catumaxomab, which represents a self-supporting system. Catumaxomab's efficacy and safety have been demonstrated in a pivotal phase II/III study and supporting phase I/II studies. It is administered as four intraperitoneal (i.p.) infusions on days 0, 3, 7, and 10 at doses of 10, 20, 50, and 150mug, respectively. Catumaxomab has been approved in the European Union since April 2009 for the i.p. treatment of malignant ascites (MA) in patients with EpCAM-positive carcinomas where standard therapy is not available or no longer feasible. Catumaxomab is the first trAb and the first drug worldwide to be approved specifically for the treatment of MA. It is in clinical trials in a number of other indications including ovarian and gastric cancer. Alternative routes of administration are also under evaluation to further exploit the therapeutic potential of catumaxomab in EpCAM-positive carcinomas.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Catumaxomab Epithelial cell adhesion molecule Protein Humans NoLigandDetails Catumaxomab High affinity immunoglobulin gamma Fc receptor I Protein Humans YesAgonistDetails Catumaxomab Low affinity immunoglobulin gamma Fc region receptor II-a Protein Humans YesAgonistDetails Catumaxomab Low affinity immunoglobulin gamma Fc region receptor III-A Protein Humans YesAgonistDetails Catumaxomab Low affinity immunoglobulin gamma Fc region receptor III-B Protein Humans YesAgonistDetails Catumaxomab T-cell surface glycoprotein CD3 epsilon chain Protein Humans YesAgonistDetails