Bavituximab
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Overview
Bavituximab is a chimeric Anti-PS monoclonal antibody analog which is used to potentially treat cancers and viral infections. It binds to phosphatidylserine and other exposed host cell lipids when induced by cellular stress. Additional analogs in the class include 3G4, 2aG4, 9d2 and Hu3g4.
Bavituximab binds to various aminophospholipids and is dependent on interaction with plasma protein beta2-glycoprotein 1 to mediate binding.
These target aminophospholipids, usually residing only on the inner leaflet of the plasma membrane of cells are purportedly only exposed in virally infected, damaged or malignant cells.
The drug’s binding to phospholipids, alerts the body’s immune system to attack the tumor endothelial cells, Thrombosing the tumors vascular network and/or attacking free floating virally infected and metastatic cells while potentially minimizing side effects in healthy tissues.
Antibody-mediated targeting of "inside-out" anionic phospholipids in viral disease
Melina Soares, Sameer Syed, Gustavo Barbero and Philip E Thorpe Pharmacology, University of Texas Southwestern Medical Center, 2201 Inwood Road, NC7.304, MC 9041, Dallas, TX, 75390
J. Immunol., Apr 2007; 178: 47.21.
Abstract
The anionic phospholipid phosphatidylserine (PS) is found exclusively in the inner leaflet of the plasma membrane of resting mammalian cells. We hypothesized that certain events that occur during virus replication (eg cell activation or membrane rearrangement) would trigger the exposure of anionic phospholipids on the outer surface of virus- infected cells and subsequently on the enveloped viruses that bud out of these virus- infected cells. We further hypothesized that these exposed anionic phospholipids would serve as targets for anti-viral therapy. We demonstrate here that anionic phospholipids become exposed on the enveloped Pichinde Virus (a model virus for Lassa Fever virus, a potential bioterrorism agent) and on Pichinde virus-infected cells. To detect anionic phospholipids, we used a chimeric monoclonal antibody, bavituximab, that binds anionic phospholipids in a B2-glycoprotein I dependent manner. We show that bavituximab treatment is able to cure overt disease in guinea pigs lethally infected with Pichinde virus. Bavituximab treatment reduced the amounts of virus in multiple tissues and caused direct clearance of virus from the blood. Direct clearance of free virus and antibody-dependent cellular cytotoxicity of virus-infected cells appear to be the major mechanisms that contribute to the anti-viral effect of bavituximab. Bavituximab-treated survivors were immune to reinfection. Furthermore, the murine version of bavituximab, 3G4, shows therapeutic efficacy in a lethal murine model for human cytomegalovirus. Our study demonstrates the promise of anionic phospholipids as targets for new broad-spectrum anti-viral drugs.