Engineered Anthrax Toxin May Boost Chemotherapy Regimen

The combination of engineered anthrax toxin proteins and current chemotherapy drugs may help treat cancerous tumors.

Bacillus anthracis is the bacterium responsible for causing anthrax disease and produces a toxin made of 3 proteins that are non-toxic individually. The proteins can be engineered to suppress tumor growth, and therefore are seen as a potential cancer therapy; however, how the anthrax toxin proteins are able to control tumor growth was unclear.

In a study published in the Proceedings of the National Academy of Sciences, researchers used mouse models to demonstrate how anthrax toxin proteins specifically target the cells that line the inner walls of blood vessels and feed the tumor.

These proteins are able to reach the cells through the surface receptor CMG2 and prevent the cells from reproducing. Additionally, the toxins target host-derived blood vessel cells instead of targeting the tumor cells themselves, and could therefore be an effective strategy for an array of tumor types.

However, researchers found that additional courses of treatment were ineffective because the immune system produces antibodies in response to the anthrax toxin proteins. To overcome this hurdle, researchers tested whether a regimen of chemotherapy drugs pentostatin and cyclophosphamide (PC) could block the production of antibodies that neutralize the anthrax toxin proteins in their mouse models.

During the study, mice were inoculated with tumors and treated with either saline (placebo), anthrax toxin protein therapy, PC, or a combination of PC and anthrax toxin protein therapy.

The results of the study showed that after 4 cycles of therapy lasting 42 days, all of the mice that received the combined regimen of anthrax toxin protein therapy plus PC were alive. Additionally, the combination regimen group were found to have no detection of any neutralizing antibodies, even after the fourth round of therapy.

Mice that were in the other regimen groups had to be euthanized because of tumor growth. Researchers stated that the study’s findings showed the combination of PC and anthrax toxin protein therapy had durable, anti-tumor effects that should be explored further.