Anthrax is new drug delivery vehicle

Anthrax doesn’t seem like the go-to vehicle for delivering cancer drugs, but researchers from MIT have engineered the bacteria to do just that. By disarming Bacillus anthracis and loading it with antibody mimics, researchers have uncovered a new way to deliver drugs to kill cancer cells by disrupting specific proteins inside the cells. “Anthrax toxin is a professional at delivering large enzymes into cells,” said Bradley Pentelute, Pfizer-Laubauch Career Development Assistant Professor of Chemistry. “We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells.” Protective antigen (PA), one of three main components of the anthrax toxin, binds to receptors called TEM8 and CMG2 which are found on most mammalian cells. Once it attaches to the cell, it forms a docking site for two other anthrax proteins – lethal factor (LF) and edema factor (EF) – which are responsible for the bacteria’s toxic activities. To render the bacteria harmless, but still able to penetrate cells, researchers removed the toxic sections of LF and EF and replaced these with antibody mimics, which were able to hitch a ride into the cells through the PA channels. These antibody mimics are based on protein scaffolds which are smaller than antibodies but conserve their structural diversity and can be designed to target different proteins inside a cell. In this study researchers successfully targeted several proteins including Bcr-Abl, which causes chronic myeloid leukaemia, and hRaf-1, a protein overactive in many cancers. Cancer cells in which these proteins were disrupted underwent apoptosis. “We show for the first time that PA can deliver bioactive antibody mimics to disrupt intracellular protein-protein interactions,” the researchers wrote in ChemBioChem. “This technology adds a useful tool to expand these agents to the intracellular milieu.” The team are now testing their approach to treat tumours in mice, and establishing ways to deliver antibodies to specific types of cell. Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen