Scientists devise powerful new method for finding therapeutic antibodies

Scientists at The Scripps Research Institute have found a new technique that should greatly speed the discovery of medically and scientifically useful antibodies, immune system proteins that detect and destroy invaders such as bacteria and viruses. New methods to discover antibodies are important because antibodies make up the fastest growing sector of human therapeutics; it is estimated that by 2014 the top-three selling drugs worldwide will be antibodies.

The new technique, described in an article this week published online ahead of print by the journal Proceedings of the National Academy of Sciences, enables researchers to search large libraries of antibodies and quickly select the ones with a desired biological effect. It also provides for the creation of unusual, asymmetric antibodies whose capabilities extend beyond those of natural antibodies. The Scripps Research scientists demonstrated the power of the technique by using it to find an asymmetric antibody that almost perfectly mimics the activity of erythropoietin (EPO), a medically valuable hormone.

''Traditionally we've looked at antibodies as tools for binding to specific targets, but we should view them more generally, as tools for probing and altering functions in cells,'' said Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and member of the Department of Molecular Biology at Scripps Research who led the new study.

Lab-grown antibodies already represent a major part of the ongoing biotechnology revolution. Used as scientific probes or medical therapies, they recreate the versatility of natural antibodies, which are produced by immune cells in a vast diversity to bind to highly specific shapes on viruses, bacteria, and other targets.

Two decades ago, Lerner and his laboratory at Scripps Research, in parallel with the group of Sir Gregory Winter at the Laboratory of Molecular Biology in Britain, developed the first techniques for generating very large libraries of combinatorial antibodies and quickly isolating those that can bind to a desired target. Since then, such techniques have been used to find antibodies to treat cancer, arthritis, transplant rejection, and other conditions. Humira, an anti-inflammatory antibody that was discovered this way, is expected to be the world's top-selling drug this year. Belimumab (Benlysta) was approved by the US Food and Drug Administration in 2011 to treat lupus, becoming the first new drug to treat the chronic, life-threatening inflammatory disease in more than 50 years.

Current antibody-discovery techniques have one big drawback, however. Although they can rapidly find antibodies that bind tightly to a known target, they can't rapidly determine which of those antibodies has useful biological activity.