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Scripps Research scientists devise powerful new method for finding therapeutic antibodies
Date:9/11/2012

lecular 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. An antibody may bind tightly to a virus without affecting the virus's ability to infect cells, for example, or it may bind to a cellular receptor without activating that receptor. With current techniques, determining the overall biological effect of a target-binding antibody typically requires further, painstaking analysis.

A More Direct Path

In the new study, Lerner and his postdoctoral researcher Hongkai Zhang sought a method for rapidly finding antibodies that have a desired effect on cells, not just a desired ability to bind to a target. As a proof of principle, they aimed to discover an antibody that could mimic the activity of EPO, a hormone that stimulates red blood cell production. Drugs that mimic EPO's effect are commonly used to treat anemia and related conditions.

Zhang began by using traditional techniques to quickly sift through a large antibody library to find tens of thousands of antibodies that bind tightly to the EPO receptor. He then stepped beyond traditional techniques, by taking the genes that encoded these EPO-receptor-binding a
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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