Could anthrax toxin be used to treat tumors? Yes, according to the authors of a study in mBio this week. They altered anthrax toxin to deliver it's potent cargo only to cells that carry a type of receptors that are enriched on several types of tumors. The altered anthrax toxin effectively attached, deposited pore-making proteins in the cell, and shuttled toxic enzymes through the newly made pores.
As we all learned back in 2001, anthrax is not something you'd want to sprinkle on your breakfast cereal. Its toxin is composed of three parts: the lethal factor, the edema factor, and the protective antigen. The protective antigen binds to surface receptors on human cells and creates pores that fold and transport lethal factor and edema factor enzymes into the cell. Once inside, these effector proteins unfold and go about their business of modifying their various targets.
An adaptable 'vehicle'
Mechaly et al. treated the anthrax protective antigen as an adaptable vehicle for delivering proteins into the cytosolic compartment of human cells. They mutated two residues within the protective antigen and fused each of two different receptor-binding proteins to the mutated protein. The resulting fusion proteins, one that binds human epidermal growth factor and one that binds diptheria-toxin receptors, effectively delivered their payloads of lethal factors and edema factors to targeted cells and not to cells that lacked the appropriate receptors.
Interestingly, the receptor for human epidermal growth factor, here targeted for toxin delivery, is enriched on several types of tumors, making the protective antigen- epidermal growth factor a potential treatment option. According to the authors, other ligands whose receptors are enriched on the target cells of choice would also be candidates for fusion to anthrax toxin.