Catumaxomab
Encyclopedia
Catumaxomab 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
).
. Fresenius Biotech conducted clinical trial
s and filed the drug for approval with the European Medicines Agency
(EMA). It was approved in Europe on 20 April 2009.
.
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.
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.
) 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
.
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.
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
-mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
hybrid monoclonal antibody which is used to treat malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
, a condition occurring in patients with metastasizing
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
cancer. It binds to antigens CD3 and EpCAM. It is in clinical trials in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
currently and is used in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
. It was developed by Fresenius Biotech and Trion Pharma (Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
).
History
Catumaxomab was developed by Trion Pharma, based on preliminary work by the Helmholtz Zentrum MünchenHelmholtz Zentrum München
The Helmholtz Zentrum München is a member of the Helmholtz Association of German Research Centres and is responsible for studying environmental health issues. Founded in 1964, it is a joint project of the Federal Ministry of Education and Research and Bavaria's Finance Ministry...
. Fresenius Biotech conducted clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s and filed the drug for approval with the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
(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 cavityAbdominal cavity
The abdominal cavity is the body cavity of the human body that holds the bulk of the viscera. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is the thoracic diaphragm , and its oblique floor is the pelvic inlet...
.
Application
The usual treatment of malignant ascites is to puncture the peritoneumPeritoneum
The peritoneum is the serous membrane that forms the lining of the abdominal cavity or the coelom — it covers most of the intra-abdominal organs — in amniotes and some invertebrates...
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, nauseaNausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
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 chainImmunoglobulin light chain
]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
) 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
Fc receptor
An Fc receptor is a protein found on the surface of certain cells - including natural killer cells, macrophages, neutrophils, and mast cells - that contribute to the protective functions of the immune system....
on accessory cells like other antibodies, which has led to calling the drug a trifunctional antibody
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 accessory cells like conventional monospecific...
.
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 cellAntigen-presenting cell
An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...
like a macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
, a natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
or a dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
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.