Monoclonal antibody | |
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Type | Trifunctional antibody |
Source | Rat/mouse hybrid |
Target | EpCAM, CD3 |
Clinical data | |
Trade names | Removab |
AHFS/Drugs.com | International Drug Names |
License data | |
Routes of administration | intraperitoneal infusion |
ATC code | |
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Catumaxomab [1] (trade name Removab) is a rat-mouse hybrid monoclonal antibody which is used to treat malignant ascites, a condition occurring in people with metastasizing cancer. It binds to antigens CD3 and EpCAM. It was developed by Fresenius Biotech and Trion Pharma (Germany).
The drug is used for the treatment of malignant ascites in people with EpCAM-positive cancer if a standard therapy is not available. [2] [3] 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. [4]
Common adverse effects include fever, nausea and vomiting. Fever and pain should be controlled by giving NSAIDs, analgetics or antipyretics before application of catumaxomab. [5] All side effects were fully reversible in studies. Most are caused by the liberation of cytokines. [2]
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 people with cancer. [2] [6] [7]
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 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. [8] 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. [9] In 2013, catumaxomab was voluntarily withdrawn from the US market and in 2017 in the EU market for commercial reasons. [10] The product had not been marketed in the EU since 2014. [11]
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.
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CD3 is a protein complex and T cell co-receptor that is involved in activating both the cytotoxic T cell and T helper cells. It is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with the T-cell receptor (TCR) and the CD3-zeta (ζ-chain) to generate an activation signal in T lymphocytes. The TCR, CD3-zeta, and the other CD3 molecules together constitute the TCR complex.
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A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzeimer's disease.
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, proliferation, and differentiation. Additionally, EpCAM has oncogenic potential via its capacity to upregulate c-myc, e-fabp, and cyclins A & E. Since EpCAM is expressed exclusively in epithelia and epithelial-derived neoplasms, EpCAM can be used as diagnostic marker for various cancers. It appears to play a role in tumorigenesis and metastasis of carcinomas, so it can also act as a potential prognostic marker and as a potential target for immunotherapeutic strategies.
Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation. While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.
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Daratumumab, sold under the brand name Darzalex, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.
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