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 journal Nature, 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.”
“Neo-2/15 has therapeutic properties that are at least as good as or better than naturally occurring IL-2, but it was computationally designed to be much less toxic,” said another lead author, Umut Ulge, an internal medicine physician and IPD biochemist.
