Phosphatidylserine (PS) and other anionic
phospholipids, which become exposed on the surface of proliferating endothelial cells,
tumor cells and certain leukocytes, have been used as targets for the development of clinical-stage
biopharmaceuticals. One of these products (
bavituximab) is currently being investigated in Phase 3 clinical trials. There are conflicting reports on the ability of
bavituximab and other
antibodies to recognize PS directly or through beta-2
glycoprotein 1, a
serum protein that is not highly conserved across species. Here, we report on the generation and characterization of two fully human
antibodies directed against
phosphatidylserine. One of these
antibodies (PS72) bound specifically to
phosphatidylserine and to
phosphatidic acid, but did not recognize other closely related
phospholipids, while the other antibody (PS41) also bound to
cardiolipin. Both PS72 and PS41 stained 8/9 experimental
tumor models in vitro, but both
antibodies failed to exhibit a preferential
tumor accumulation in vivo, as revealed by quantitative biodistribution analysis. Our findings indicate that anionic
phospholipids are exposed and accessible in most
tumor types, but cast doubts about the possibility of efficiently targeting
tumors in vivo with PS-specific
reagents.