Catumaxomab: clinical development and future directions

Abstract

Catumaxomab, a monoclonal bispecific trifunctional antibody, was approved in the European Union in April 2009 for the intraperitoneal treatment of patients with malignant ascites. The marketing authorization holder Fresenius Biotech GmbH developed catumaxomab (Removab(®)) together with its partner TRION Pharma GmbH, Germany. It is the first substance worldwide with a regulatory label for the treatment of malignant ascites due to epithelial carcinomas. Since the peritoneum is of mesothelial origin and therefore lacks EpCAM expression, the intraperitoneal administration of catumaxomab is an attractive targeted immunotherapeutic approach. Catumaxomab is able to destroy EpCAM positive tumor cells in the peritoneal cavity known as the main cause of malignant ascites. In addition, catumaxomab is a potential therapeutic option for several primary tumors since the EpCAM molecule is expressed on the majority of epithelial carcinomas. This review focuses on the clinical development of catumaxomab and indicates future directions.

Figure 1

The postulated mechanism of action of catumaxomab: The intact trifunctional antibody catumaxomab accelerates the recognition and destruction of tumor cells by different immune cells. ADCC, antibody-dependent cellular toxicity; DC-CK1, dendritic cell cytokine 1; iL, interleukin; IFNγ, interferon gamma; TnFα, tumor necrosis factor alpha; LFA, lymphocyte function antigen; nK, natural killer; GM-CSF, granulocyte monocyte colony stimulating factor.

Figure 2

Ascites symptoms: The benefit of the catumaxomab therapy was also confirmed in the assessment of ascites symptoms.

Figure 3

Incidence of pyrexia, nausea and vomiting: The expected and manageable cytokine release related symptoms did not increase during treatment.