Catumaxomab

Catumaxomab (trade name Removab) is a rat-mouse hybrid monoclonal antibody which is used to treat malignant ascites, a condition occurring in patients with metastasizing cancer. It binds to antigens CD3 and EpCAM. It is in clinical trials in the United States currently and is used in Europe. It was developed by Fresenius Biotech and Trion Pharma (Germany).

History
Catumaxomab was developed by Trion Pharma, based on preliminary work by the Helmholtz Zentrum München. Fresenius Biotech conducted clinical trials and filed the drug for approval with the European Medicines Agency (EMA). It was approved in Europe on 20 April 2009.

Indications
The drug is approved for the treatment of malignant ascites in patients with EpCAM-positive cancer if a standard therapy is not available. Ascites is an accumulation of fluid in the abdominal cavity.

Application
The usual treatment of malignant ascites is to puncture the peritoneum to let the accumulated fluid drain out. After the puncture, catumaxomab is given as an intraperitoneal infusion. The procedure is repeated four times within about eleven days. It has been shown that puncture free survival can be increased from 11 to 46 days with this treatment.

Adverse effects
Common adverse effects include fever, nausea and vomiting. Fever and pain should be controlled by giving NSAIDs, analgetics or antipyretics before application of catumaxomab. All side effects were fully reversible in studies. Most are caused by the liberation of cytokines.

Chemical structure
Catumaxomab consists of one "half" (one heavy chain and one light chain) of an anti-EpCAM antibody and one half of an anti-CD3 antibody, so that each molecule of catumaxomab can bind both EpCAM and CD3. In addition, the Fc-region can bind to an Fc receptor on accessory cells like other antibodies, which has led to calling the drug a trifunctional antibody.

Mechanism of action
Many types of cancer cells carry EpCAM (epithelial cell adhesion molecule) on their surface. By binding to such a cell via one arm, to a T lymphocyte via the other arm and to an antigen-presenting cell like a macrophage, a natural killer cell or a dendritic cell via the heavy chains, an immunological reaction against the cancer cell is triggered. Removing cancer cells from the abdominal cavity reduces the tumour burden which is seen as the cause for ascites in cancer patients.