Sic Anthrax on Cancer
Anthrax bacteria produce one of the most potent sets of toxins, a one-two-three punch that knocks out the immune system allowing the bacteria to grow unchecked in the blood. Anthrax bacteria were of course tamed by scientists in The Highest Frontier. Today, actual scientists are engineering the anthrax toxin to selectively knock out cancer cells.
The PA component of the toxin is a ring-shaped pore of repeating subunits (above). The pore allows insertion of toxic enzymes across a membrane into the cytoplasm of the human cell. So the researchers engineered the protein for a different function, by changing its DNA coding sequence:
(1) First, they mutated the DNA so as to substitute two key amino acids with different ones (such as asparagine to alanine). The altered PA ring was purified from recombinand E. coli cells. The purified mutant PA toxin no longer binds to the usual receptor protein on the surface of a mammalian cell.
(2) Next, the gene was mutated again by fusion with a gene encoding epidermal growth factor (EGF). Now the protein PA-EGF was added to tissue culture cell called A431 cells, a line of epidermoid carcinoma which express high levels of EGF receptor protein. EGF receptor protein is typically expressed by cancer cells (which are thereby stimulated to grow by EGF).
(3) The PA-EGF mediated killing of the cultured cells by the anthrax component “lethal factor” (LF) which was fused to diptheria toxin to kill the cells quicker. Now the PA-EGF pore transported the LF-diptheria-toxin into the cytoplasm and killed the cells.
Of course, various controls showed that all the components were necessary, and that cancer cells were killed specifically. It will be interesting to see if this trick can be made into a practical therapy.