Bavituximab
Encyclopedia
Bavituximab is a chimeric monoclonal antibody designed for the treatment of cancer
s and viral infections.
which is exposed on the surface of certain atypical animal cells, including tumour cells and cells infected with any of six different families of virus. These viral families contain the viruses hepatitis C, influenza A and B, HIV 1 and 2, measles, respiratory syncytial virus and pichinde virus, which is a model for the deadly Lassa hemorrhagic fever. Other cells are not affected since phosphatidylserine normally is only intracellular
.
Bavituximab binds to various aminophospholipids and is dependent on interaction with plasma protein beta-2 glycoprotein I to mediate binding.
These target aminophospholipids, usually residing only on the inner leaflet of the plasma membrane of cells, become exposed in virally infected, damaged or malignant cells, and more generally in most cells undergoing the process of apoptosis.
The antibody's binding to phospholipid
s alerts the body’s immune system
to attack the tumor endothelial cells, thrombosing
the tumor's vascular network
and/or attacking free floating virally infected and metastatic cells while potentially minimizing side effects in healthy tissues.
has yielded median progression-free survival (PFS) data of 7.4 months, a best overall response rate of 61% (28 of 46 patients) with 11% (5 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving docetaxel alone, which showed an objective response rate of only 41% with no complete responses. Median overall survival figures are not yet available.
A phase II trial of bavituximab used with paclitaxel
and carboplatin
chemotherapy against advanced breast cancer
has yielded median progression-free survival (PFS) data of 6.9 months, a best overall response rate of 74% (34 of 46 patients) with 9% (4 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving paclitaxel and carboplatin alone, which showed a median PFS of 4.8 months, an objective response rate of 62%.) Median overall survival figures are not yet available.
Another phase II study of bavituximab plus paclitaxel and carboplatin is being conducted in untreated locally advanced or metastatic non-small cell lung cancer.
s in the class include 3G4, 2aG4, 9d2 and Hu3g4.
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s and viral infections.
Mechanism of action
Bavituximab binds to phosphatidylserinePhosphatidylserine
Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...
which is exposed on the surface of certain atypical animal cells, including tumour cells and cells infected with any of six different families of virus. These viral families contain the viruses hepatitis C, influenza A and B, HIV 1 and 2, measles, respiratory syncytial virus and pichinde virus, which is a model for the deadly Lassa hemorrhagic fever. Other cells are not affected since phosphatidylserine normally is only intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
.
Bavituximab binds to various aminophospholipids and is dependent on interaction with plasma protein beta-2 glycoprotein I to mediate binding.
These target aminophospholipids, usually residing only on the inner leaflet of the plasma membrane of cells, become exposed in virally infected, damaged or malignant cells, and more generally in most cells undergoing the process of apoptosis.
The antibody's binding to phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s alerts the body’s immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to attack the tumor endothelial cells, thrombosing
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
the tumor's vascular network
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
and/or attacking free floating virally infected and metastatic cells while potentially minimizing side effects in healthy tissues.
Clinical trials
A phase II trial of bavituximab used with docetaxel against advanced breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
has yielded median progression-free survival (PFS) data of 7.4 months, a best overall response rate of 61% (28 of 46 patients) with 11% (5 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving docetaxel alone, which showed an objective response rate of only 41% with no complete responses. Median overall survival figures are not yet available.
A phase II trial of bavituximab used with paclitaxel
Paclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a U.S. National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it taxol...
and carboplatin
Carboplatin
Carboplatin, or cis-Diammineplatinum is a chemotherapy drug used against some forms of cancer...
chemotherapy against advanced breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
has yielded median progression-free survival (PFS) data of 6.9 months, a best overall response rate of 74% (34 of 46 patients) with 9% (4 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving paclitaxel and carboplatin alone, which showed a median PFS of 4.8 months, an objective response rate of 62%.) Median overall survival figures are not yet available.
Another phase II study of bavituximab plus paclitaxel and carboplatin is being conducted in untreated locally advanced or metastatic non-small cell lung cancer.
Other monoclonal antibodies targeting phospholipids
Additional analogFunctional analog
Functional analogs , are compounds that have similar physical, chemical, biochemical, or pharmacological properties. An example of a functional analog is morphine and heroin. Functional analogs are not necessarily also structural analogs with a similar chemical structure...
s in the class include 3G4, 2aG4, 9d2 and Hu3g4.