MIPS Project Challenge:
PharmAthene sought to evaluate the mechanism of action of Valortim, a human monoclonal antibody directed against anthrax Protective Antigen (PA) toxin.

Project Scope:
In the aftermath of the bioterrorist event with anthrax in 2001, the need for more effective therapeutic agents for treating individuals exposed to anthrax became apparent. PharmAthene, in collaboration with Medarex (now BMS), developed a human monoclonal antibody, Valortim, designed to target the Bacillus anthracis (BA) protective antigen (PA) that has demonstrated efficacy in the prevention of anthrax lethality in rabbits and non-human primates. Since a mechanism of action for Valortim appears to be unique compared to other anthrax antibodies, this MIPS project focused on evaluating the mechanisms that may result in the protection of human cells from the anthrax toxin. The university team evaluated the mechanism by which Valortim enhances the ability of human dendritic cells (hDCs) to kill BA spores, as well as assessed its ability to inhibit anthrax toxins and to alter the intracellular localization of BA spores in hDCs. Human T cell responses in the presence and absence of Valortim were also evaluated. Together, these studies have been significant in defining how Valortim may provide protection in humans, an important progression in the Valortim research program.