Scientists at UW Medicine’s Institute for Protein Design have created a new protein that mimics the action of a key immune regulatory protein, interleukin 2 (IL-2). IL-2 is a potent anticancer drug and an effective treatment for autoimmune disease, but its toxic side effects have limited its clinical usefulness.
In a paper in the Jan. 10 issue of the journalNature, the researchers report using computer programs to design a protein that they have shown in animal models to have the same ability to stimulate cancer-fighting T-cells as the naturally occurring IL-2, but without triggering harmful side effects. Read the paper and the Nature News & Views commentary.
The achievement opens new approaches to the design of protein-based therapeutics for the treatment of cancer, autoimmune diseases and other disorders, the researchers said.
The new protein has been dubbed Neo-2/15 because, in addition to mimicking the effect of IL-2, the protein can also mimic the effect of another interleukin, IL-15, which is being studied as another possible anticancer immunotherapy.
“People have tried for 30 years to alter IL-2 to make it safer and more effective, but because naturally occurring proteins tend not to be very stable, this has proved to be very hard to do,” said a lead author of the paper, Daniel-Adriano Silva, an IPD biochemist. “Neo-2/15 is very small and very stable. Because we designed it from scratch, we understand all its parts, and we can continue to improve it making it even more stable and active.”