Researchers have modified one of the most hazardous bio-weapon to actually save lives. Yes, you read that right, they have modified the strains of anthrax toxin for delivering antibody drugs to kill cancer cells.
Bacillus anthracis can inject toxin efficiently into the host which can possibly lead to death. A research team at MIT has hijacked their delivery system for administering cancer drugs.
Anthrax toxin can be used for delivery of two proteins known as antibody mimics, which kills cancer cells by disrupting specific proteins inside the cells.
Hitching for a ride
Antibodies is a natural protein that the body produces to bind to foreign invaders. It is a rapidly growing area of pharmaceutical development. Scientists have designed new antibodies which can disrupt proteins such as the HER2 receptor, found on the surfaces of some cancer cells. Herceptin, which is the resulting drug has been successfully used for the treatment of breast tumors that overexpress the HER2 receptor.
There are several antibody drugs developed to target other receptors that are found in cancer cell surface. But it is limited, as it is very difficult to penetrate the protein inside the cell
One of the major setbacks in biotechnology is that there really doesn’t exist a technology to deliver antibodies into cells.
To solve this problem scientists have been working for decades with anthrax toxin to understand how does this toxin get into the cell. Now researchers have started exploring the possibility of mimicking this system for delivery of small protein molecules as vaccines.
Anthrax toxin has three major components. One is a protein called protective antigen (PA), that binds to receptors called TEM8 and CMG2 that are found in most mammalian cells. Once PA attaches to the cell, it forms a docking site for two anthrax proteins called lethal factor (LF) and edema factor (EF). These proteins are pumped into the cell through a narrow pore and disrupt cellular processes, often resulting in the cell’s death.
However, this system can be made harmless by removing the sections of the LF and EF proteins that are responsible for their toxic activities, leaving behind the sections that allow the proteins to penetrate cells.
The researchers then replaced the toxic regions with antibody mimics, allowing these cargo proteins to catch a ride into cells through the PA channel.
A prominent advancement
The antibody mimics are based on protein scaffolds which are smaller than antibodies but still maintain structural diversity and it can be designed to target different proteins inside a cell. Here the researchers successfully targeted several proteins, that includes Bcr-Abl-causes chronic myeloid leukemia; cancer cells in which that protein was disrupted underwent programmed cell suicide. They also successfully blocked hRaf-1, a protein that is overactive in many cancers.
This technique has led to prominent advancement in the drug delivery field. This technology in comparison to traditional cell-penetrating peptides have proven better result and is highly anticipated in the market.
The testing of this approach for treating tumors in mice is going on and is also working on ways to deliver the antibodies to specific types of cells.