New 'library' will aid the detection of antibodies

A library containing one billion human antibodies on the surface of yeast cells has been created by US Department of Energy scientists and K. Dane Wittrup, JR Mares Professor of Chemical Engineering and Bioengineering at MIT. The work will not only speed up the search for new antibodies, but also promises to make the hunt less expensive.

'We have captured a broad sample of the antibody diversity present in adult humans, and expressed it on the surface of yeast cells in a format suitable for quantitative screening,' said Wittrup. 'The technology provides a robust and direct route to the isolation of useful antibodies outside a living body. As a result, it could replace the need to produce antibodies within animals, such as mice. It also opens up new possibilities for rapidly designing medical treatments more acceptable to the human immune system.'

According to Michael Feldhaus, who led the team of scientists at the Department of Energy's Pacific Northwest National Laboratory (PNNL), the antibody library offers many advantages over traditional approaches. PNNL's method of generating synthetic antibodies uses high-speed flow cytometers to sort cells. Most importantly, by incorporating Wittrup's yeast surface display method, PNNL scientists can readily modify how an antibody binds to proteins. Being able to increase how tightly a protein and antibody bind together, for example, could increase antibody effectiveness for detecting pathogens or disease.

Wittrup originally developed the yeast surface dis-play to improve the binding of antibodies to chemicals while working at the University of Illinois in the late 1990s. Now he uses PNNL's antibody library with his display platform in studies mainly directed at development of novel cancer therapeutics.