Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that blocks PS-mediated immunosuppression by multifocal reprogramming of immune cells in the tumor microenvironment to support immune activation.1 PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but “flips” and becomes exposed on the outside of cells that line tumor blood vessels, creating a specific target for anticancer treatments. PS-targeting agents block PS-mediated immunosuppression by multifocal reprogramming of immune cells in the tumor microenvironment to support immune activation.1
Preclinical data demonstrate that bavituximab:
After binding exposed PS in tumors, bavituximab engages Fc-γ receptors on tumor-promoting myeloid-derived suppressor cells (MDSCs), M2-like tumor-associated macrophages (which fail to differentiate into M1-like tumor-killing macrophages and natural killer cells), and immature dendritic cells, leading to multiple immunostimulatory changes in the tumor environment.2 These changes include:
Thus, antibody-mediated PS blockade reduces the levels of MDSCs, transforming growth factor beta (TGF-β) and IL-10 and increases the levels of TNF-α and IL-12.1 M1 macrophages contribute to tumor destruction through antibody-dependent cellular cytotoxicity, while mature dendritic cells educate T cells, inducing tumor-specific cytotoxic T-cell responses.2,3