Catumaxomab

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Catumaxomab ?
Monoclonal antibody
Type Trifunctional antibody
Source Rat/mouse hybrid
Target EpCAM, CD3
Clinical data
Trade names Removab
AHFS/Drugs.com International Drug Names
Licence data EMA:Link
Legal status
  • Prescription only
Routes intraperitoneal infusion
Identifiers
CAS number 509077-98-9 N
ATC code L01XC09
Chemical data
Formula ?
 N (what is this?)  (verify)

Catumaxomab[1] (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[edit]

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.[2]

Indications[edit]

The drug is approved for the treatment of malignant ascites in patients with EpCAM-positive cancer if a standard therapy is not available.[3][4] Ascites is an accumulation of fluid in the abdominal cavity.

Application[edit]

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.[5]

Adverse effects[edit]

Common adverse effects include fever, nausea and vomiting. Fever and pain should be controlled by giving NSAIDs, analgetics or antipyretics before application of catumaxomab.[6] All side effects were fully reversible in studies. Most are caused by the liberation of cytokines.[7]

Chemical structure[edit]

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.svg


Mechanism of action[edit]

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.[7][8][9]

Catumaxomab mechanism.svg


References[edit]

  1. ^ Linke, Rolf; Anke Klein and Diane Seimetz (2010). "Catumaxomab: Clinical development and future directions". mAbs 2 (2): 129–136. doi:10.4161/mabs.2.2.11221. 
  2. ^ TRION Pharma: Trifunctional Antibody Catumaxomab Kills Cancer Stem Cells
  3. ^ European Public Assessment Report for Removab
  4. ^ Heiss u.a.: The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: results of a prospective randomized phase II/III trial. Int J Cancer. (2010) 127: 2209-2221
  5. ^ Lordick, F; Ott, K; Weitz, J; Jäger, D (2008). "The evolving role of catumaxomab in gastric cancer". Expert Opinion on Biological Therapy 8 (9): 1407. doi:10.1517/14712598.8.9.1407. PMID 18694358.  edit
  6. ^ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2009
  7. ^ a b Assessment Report for Removab
  8. ^ Capital Market Day Fresenius Biotech: Fresenius concentrates biotechnology activities on antibody and innovative cell therapies
  9. ^ Ruf, P.; Gires, O.; J, M.; Fellinger, K.; Atz, J.; Lindhofer, H. (2007). "Characterisation of the new EpCAM-specific antibody HO-3: implications for trifunctional antibody immunotherapy of cancer". British Journal of Cancer 97 (3): 315–321. doi:10.1038/sj.bjc.6603881. PMC 2360319. PMID 17622246.  edit

External links[edit]