Exposing Epitopes Without Exposing People

The flaws that mar proteins as drugs would be a lot easier to eliminate, or at least reduce, were it not for the one thing that gives protein engineers fits: allergic reactions. The protein engineer's doctoring arts are balm for many a malady, but not allergic reactions. A protein too unstable, too toxic, maybe too costly to manufacture, or burdened by some other problem, changes for the better when the appropriate amino acid residues are altered. The catch is that protein engineers never know w

Written byTom Hollon

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The trouble arises when a new amino acid, together with surrounding residues, creates an allergenic peptide --a T-cell epitope--capable of triggering an immune response. Without a reliable way to predict T-cell epitopes, fixing proteins while avoiding allergic reactions requires the optimism of a high wire walker using a matchstick for a balance pole.

Now, a new technique may help engineers keep their footing. An in vitro cell-based assay,¹ developed by Marcia Stickler, David Estell, and Fiona Harding, of Genencor International, of Palo Alto, Calif., lets protein engineers find out if changing an amino acid will bring an unwanted immune response. Genencor uses the assay to ensure that proteins developed for its personal care products won't cause allergic reaction; T-cell epitopes are systematically mapped, then, one by one, eliminated without sacrificing desirable protein traits. Developers of therapeutic proteins could do the same thing before going into clinical trials.

The assay tests ...

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