Oportuzumab monatox VB4-845 is made by linking a monoclonal antibody fragment to a toxic protein that may kill cancer cells, and is a fusion protein containing humanized scFv specific for the epithelial cell adhesion molecule, Ep-CAM, a tumor cell-associated target highly expressed on carcinoma cells of epithelial origin and a truncated portion of Pseudomonas exotoxin A.
<0.001 EU per 1 μg of the peptide by the LAL method
Investigated for use/treatment in bladder cancer and head and neck cancer.
Examples of Clinical Use:
Bladder cancer and head and neck cancer
Mechanism of action:
VB4-845 binds to EpCAM (a protein on the surface of epithelial cells and some types of cancer cells). Also called anti-EpCAM-Pseudomonas-exotoxin fusion protein and Proxinium. It targets and kills Ep-CAM-positive tumors by apoptosis.
Oportuzumab monatox is an artificially synthesized monoclonal antibody targeting epidermal cell tumor antigen (EpCAM). EpCAM is a cell surface glycoprotein, which is a common marker of many solid tumor cells, including ovarian cancer, gastric cancer, liver cancer, colorectal cancer, pancreatic cancer, etc. Oportuzumab monatox is a soluble bispecific protein that can bind to EpCAM and cytotoxics, targeting cancer cells.
The structure of Oportuzumab monatox
The structure of Oportuzumab monatox consists of two parts: one is a monoclonal antibody (mAb), which contains an antigen binding site that can specifically bind to EpCAM; The other part is the toxin unit (DU), which is a specific peptide that can affect the activity of intracellular enzymes, leading to cell death. DU and mAb are interconnected through peptide bonds to form Oportuzumab monatox.
R&D History of Oportuzumab monatox
Its initial research mainly focused on helping to treat autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. With the continuous deepening of research, it has been found that Oportuzumab monatox can also be used to treat leukemia and other malignant tumors.
Oportuzumab monatox was originally developed by a British biotechnology company, GSK, in1990s, with the aim of developing a new biological drug that can treat solid tumors. The drug was sold by GSK to Columbia Laboratories in 2007. Later, Columbia Laboratories established a subsidiary, AntiCancer Inc., and continued to develop the drug. In 2019, it was approved by the Food and Drug Administration (FDA) for clinical trials.
The effect of Oportuzumab monatox
Oportuzumab monatox binds to the surface of EpCAM, and then is absorbed into the cells by Phagocyte (Eosinophil, Monocyte, etc.) in the passenger body. The toxin units in Oportuzumab monatox are released and enter the nucleus, inhibiting protein synthesis and causing cell death, thereby achieving anticancer effects.
Mechanism of action of Oportuzumab monatox
The mechanism of action of Oportuzumab monatox has two aspects. Firstly, it can accurately locate cancer cells by combining with EpCAM. Secondly, its peptide units can affect the activity of intracellular enzymes and cause cell death.
Related drugs of Oportuzumab monatox
The drug that is mainly similar to Oportuzumab monatox is Labetuzumab, with a mechanism of action similar to Oportuzumab monatox. It is also an artificially synthesized monoclonal antibody against EpCAM. Labetuzumab has completed Phase I and Phase II clinical trials and demonstrated certain anti-tumor effects in combination chemotherapy, but has not yet received FDA approval.
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