Catumaxomab (trade name Removab) is a

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' ( pack rats), ''Bandicota'' (bandicoot ...

mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

hybrid monoclonal antibody which is used to treat malignant ascites, a condition occurring in people with

metastasizing Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

cancer. It binds to antigens CD3 and EpCAM. It was developed by

Fresenius Fresenius is a German surname. Notable people with the surname include: * Carl Remigius Fresenius (1818–1897), German chemist * Christian Fresenius (1749-1811), German Jurist and writer * Eduard Fresenius ( (1874–1946), German businessman, fou ...

Biotech and Trion Pharma ( Germany).

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 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,

analgetic An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...

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

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

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 An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using ...

like a

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

, a

natural killer cell Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and repres ...

or a

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

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 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 ...

History

Catumaxomab was developed by Trion Pharma, based on preliminary work by the Helmholtz Zentrum München. Dr. Horst Lindhofer is listed at the primary inventor of the patent. Fresenius Biotech conducted clinical trials and filed the drug for approval with the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(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