Fighting Cancer With Anthrax--It's All in the Delivery

The bacteria Bacillus anthracis, is responsible for the potentially deadly infection known as anthrax. While healthcare professionals and researchers alike have gone to great lengths to treat and minimize exposure to this lethal disease, others are utilizing the bacteria's intricate machinery as a way to deliver cancer drugs.

Chemistry researchers at the Massachusetts Institute of Technology (MIT) developed a nontoxic version of the anthrax toxin to help deliver antibody proteins to cancer cells by disrupting specific proteins within the cell.

“Anthrax toxin is a professional at delivering large enzymes into cells,” says Bradley Pentelute, the Pfizer-Laubauch Career Development Assistant Professor of Chemistry at MIT." We wondered if we could render anthrax toxin nontoxic, and use it as a platform to deliver antibody drugs into cells.”

In the age of growing targeted therapy development, scientists have been able to design antibodies that can disrupt proteins, such as the HER2 receptor. However, it's very difficult to get proteins inside of cells, including cancer cells. This is where anthrax comes in.

Researchers have been trying to figure out how the anthrax toxins are actually able to cross the membrane and enter the cell. Just recently, scientists have started exploring ways in which to mimic this system via a vaccine.

The anthrax toxin has three major components: protective antigen (PA), lethal factor (LF), and edema factor (EF). Once the PA attaches to the cell receptors, it forms a site for the two anthrax proteins LF and EF. These proteins then enter the cell through a narrow pore, disrupting the cellular process and causing cell death. But, by removing the toxic activities of the cell (LF and EF), the component left behind still allows proteins to penetrate the cells. The MIT researchers ingeniously replaced the toxic regions with antibody mimics-allowing proteins to hitch a ride into the cells via the PA channel.

The antibody mimics are designed to target different proteins within the cell. For example, researchers targeted the protein Bcr-Abl, which is responsible for chronic myeloid leukemia (CML). They also successfully blocked hRaf-1, the protein found to be overactive in other various cancers.

“This work represents a prominent advance in the drug-delivery field,” says Jennifer Cochran, an associate professor of bioengineering at Stanford University." Given the efficient protein delivery Pentelute and colleagues achieved with this technology compared to a traditional cell-penetrating peptide, studies to translate these findings to in vivo disease models will be highly anticipated.”