Phosphatidylserine–β2-glycoprotein I complex (PS-β2GPI)

The Phosphatidylserine–β2-glycoprotein I (PS-β2GPI) complex is a molecular assembly formed when the plasma protein β2-glycoprotein I binds to externalized phosphatidylserine (PS) on cell surfaces (1.1.1, 1.2.1). In healthy cells, PS is sequestered to the inner leaflet of the plasma membrane, but in the tumor microenvironment, factors like hypoxia and oxidative stress trigger its exposure on the outer leaflet of tumor cells and tumor vascular endothelial cells (1.2.1, 1.3.1). This externalized PS acts as a potent immunosuppressive signal, promoting the polarization of tumor-associated macrophages toward an anti-inflammatory M2 phenotype and inhibiting dendritic cell maturation (1.1.1, 1.2.3). The PS-β2GPI complex serves as a specific target for therapeutic antibodies such as bavituximab, which bind to the complex and facilitate the reprogramming of the immune environment toward a pro-inflammatory M1 state (1.1.1, 1.1.3). This immune shift enhances the anti-tumor response and can induce antibody-dependent cellular cytotoxicity (ADCC) specifically against the tumor vasculature (1.1.2, 1.1.3). Because PS exposure is largely restricted to stressed or dying cells within the tumor, targeting this complex offers a high degree of tumor specificity while sparing healthy tissues (1.2.1, 1.4.1).

Other names

Phosphatidylserine-Apolipoprotein H complexPS-ApoH complexPS-beta2-GPI complexAnionic phospholipid-beta2-glycoprotein I complex

Binds to the PS-β2GPI complex to reverse immunosuppression in the tumor microenvironment, promoting M1 macrophage polarization and inducing antibody-dependent cellular cytotoxicity (ADCC) against tumor vascular and tumor cells.