Catumaxomab (trade name Removab) is a rat- mouse hybrid

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ...

which is used to treat

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

, a condition occurring in people with metastasizing cancer. It binds to antigens CD3 and

EpCAM Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a transmembrane glycoprotein mediating Ca2+-independent homotypic cell–cell adhesion in epithelia. EpCAM is also involved in cell signaling, migration, prol ...

. It was developed by Fresenius Biotech and

Trion Pharma Trion may refer to: * Trion, Georgia, a town in Chattooga County, Georgia, United States *Alpha Trion, the name of several fictional characters in the various ''Transformers'' universes *Trion (neural networks), a localized group of neurons in the c ...

(

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...

Medical use

The drug is used for the treatment of malignant ascites in people with EpCAM-positive cancer if a standard therapy is not available. Ascites is an accumulation of fluid in the

peritoneal cavity The peritoneal cavity is a potential space between the parietal peritoneum (the peritoneum that surrounds the abdominal wall) and visceral peritoneum (the peritoneum that surrounds the internal organs). The parietal and visceral peritonea are la ...

. The usual treatment of malignant ascites is to puncture the

peritoneum The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of meso ...

to let the accumulated fluid drain out. After the puncture, catumaxomab is given as an

intraperitoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesothel ...

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 Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and vomiting. Fever and pain should be controlled by giving

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s, analgetics or

antipyretics An antipyretic (, from ''anti-'' 'against' and ' 'feverish') is a substance that reduces fever. Antipyretics cause the hypothalamus to override a prostaglandin-induced increase in temperature. The body then works to lower the temperature, which r ...

before application of catumaxomab. All side effects were fully reversible in studies. Most are caused by the liberation of cytokines.

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 A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

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 people with cancer.

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. Catumaxomab structure

History

Catumaxomab was developed by Trion Pharma, based on preliminary work by the

Helmholtz Zentrum München Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), also known as Helmholtz Munich, is a member of the Helmholtz Association of German Research Centres. It was founded in 1960 and is a joint venture by the Fede ...

. Dr. Horst Lindhofer is listed at the primary inventor of the patent. Fresenius Biotech conducted

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s and filed the drug for approval with the European Medicines Agency (EMA). It was approved in Europe on 20 April 2009. In 2013, catumaxomab was voluntarily withdrawn from the US market and in 2017 in the EU market for commercial reasons. The product had not been marketed in the EU since 2014.

References

External links

The trifunctional antibody catumaxomab: information for healthcare professionals
(manufacturer website) {{Monoclonals for tumors Monoclonal antibodies for tumors Experimental drugs