Entdoc,Ftm,Sulaco,Mojojo,Cigaddy---If I am reading this correctly the tumor surface as well as it's vasculature exhibits PS.Therefore Bavi should also bind the PS on tumor surfaces. If PS is not exposed on tumor surfaces to any appreciable degree what masks the tumor itself from immune system attack ?
I am a non scientist just trying to somewhat understand the science.
NYAS 5-1-12 Meeting Report - Speaker: Philip Thorpe, UTSW-MC/Dallas
HIGHLIGHTS
• Bavituximab, an antibody drug in development by Peregrine Pharm., targets PS in tumor blood vessels and can reactivate immunity to cancer cells.
• This antibody can serve as both an imaging agent and as an adjuvant treatment with other therapies.
• Bavituximab can induce tumor-specific T-cell immunity in some situations.
TARGETING TUMOR VASCULATURE
Taking advantage of the externalization of PS on tumor cells could provide new treatment strategies for cancer treatments. Philip Thorpe of UT Southwestern MC (Dallas) described preclinical & clinical studies of bavituximab, an antibody drug developed by Peregrine Pharmaceuticals that targets PS in the vasculature of tumors. As tumors develop, they create a stressful, hypoxic cellular environment that results in the formation of reactive oxygen species and the release of inflammatory cytokines. In this environment, the asymmetry of lipid distribution in the membrane of the endothelial cells that line tumor blood vessels breaks down, leading to the externalization of PS. In addition, PS is often exposed on the surface of tumor cells. As a strategy for targeting PS externalization, Peregrine Pharm. initially developed a mouse monoclonal antibody that targets PS by binding to 2 molecules of B2-glycoprotein-I that in turn bind to PS on the surface of cells. With only a single molecule of the protein, binding to the surface of cells is relatively weak, but the affinity increases by a factor of 30,000 with the addition of a second molecule of B2-glycoprotein-I. The researchers have constructed a series of antibodies that targets the tumor vasculature. Two are mouse antibodies, 3G4 & 2aG4. Bavituximab is a chimeric antibody with mouse PS binding regions fused to human IgG. The fully human antibody is known as PGN635. These antibodies localize specifically to the blood vessels in tumors, which makes them useful as imaging agents. Studies with normal tissues and various tumor types reveal that these antibodies show affinity for a range of tumor types but minimal binding to a variety of normal tissues.
