NIH researchers have pinpointed how anthrax toxin proteins suppress tumor growth: they target the epithelial cells of blood vessels feeding the tumor. Combining these proteins with chemotherapy drugs could lead to a new take on controlling cancer.
Bacillus anthracis produces a toxin that causes anthrax disease. This toxin is made up of three proteins that are nontoxic on their own and can be engineered to curb cancer growth. The NIH team showed in mouse models that the proteins specifically target the cells that line the blood vessels that keep the tumor alive, according to a statement. They stop cancer cells from reproducing by binding to a surface receptor called CMG2.
While anthrax toxins damage host cells by reacting with a protein called furin protease, the proteins used in the study have been engineered so they cannot react with any furin protease in the body, Stephen Leppla, chief of the Microbial Pathogenesis Section of the NIAID's Laboratory of Parasitic Diseases, told FierceBiotechResearch. They are instead activated by two tumor-associated proteins that are overproduced by tumor cells as well as their supplying blood vessels, thus making the anthrax proteins tumor-selective.
They hit a snag when they found the immune system produces antibodies against the anthrax toxin proteins, thus rendering further courses of treatment ineffective. To remedy this, the team decided to combine the proteins with chemotherapy drugs that could inhibit production of antibodies that neutralize the anthrax proteins, the NIH said in the statement. They divided mice with tumors into four groups: one received placebo, the second was treated with the anthrax proteins alone, the third received chemotherapy drugs alone and the fourth got the combination therapy.
After 42 days and four cycles of treatment, all of the mice in the combination group were alive, while all the other mice had to be euthanized because of tumor growth, according to the statement. And even after four courses of the combo therapy, the team did not find any neutralizing antibodies in those mice.
The study authors deemed the combo “worthy of further exploration” due to its durable antitumor effects. And because the treatment targets tumor vasculature rather than a specific type of tumor, the team believes the approach could be useful in a range of cancers.
- here's the statement
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