Viruses are skillful mutants, changing their structures or outer proteins to evade the shifting natural defenses of their targets. (This is why you have to get a flu shot every year.) Now researchers in France report using one of the most proficient mutants, HIV, to fight another intractable disease: Cancer.
Researchers at the French National Center for Scientific Research set out to study molecules that could improve the effectiveness of cancer drugs. As they explain in their paper, this process often involves screening for the desired trait using bacteria, but sometimes a molecule that works on a bacterium doesn’t work the same way on a human cell. It would be better to start out with a human cell and screen new compounds right there. To speed the process of finding these new compounds, the team worked with HIV, taking advantage of its replication machinery and proclivity for mutating.
As HIV replicates, it creates slightly new versions of itself over successive generations — this allows it to readily resist most of the drug cocktails and anti-viral treatments developed to fight it. But it could also allow HIV to serve as a sort of molecule factory, creating new iterations of compounds that work in slightly different ways.
The CNRS team modified the genome of HIV by inserting a human gene for a protein called deoxycytidine kinase (dCK). This protein is found in all cells and is important for activating anti-cancer drugs. Researchers would like to make a more potent form of dCK that would allow cancer drugs to work more effectively, which could in turn require less of them, causing fewer side effects and less toxicity.
The team multiplied this mutant HIV through several generations, yielding an entire library of mutant dCK proteins, about 80 in all. Ultimately, they found a variant that induces tumor cells to die. With just 1/300th the dose of cancer-killing drugs, this one-two protein punch is just as effective at stopping tumor growth.
This is notable for a few reasons — first, the mutated protein was shown to work in human cell cultures, eliminating several middle steps with bacteria or animals. Second, it suggests there's a way to make cancer drugs work more effectively simply by beefing up the body's internal chemistry. And finally, it suggests a new therapeutic use for one of humanity’s strongest adversaries — HIV-derived protein factories could pump out generations upon generations of new molecules and drug compounds to help alleviate a wide range of illnesses. The French team’s paper appears in the journal PLoS Genetics.
