New Polymer Coat Gives Protein Immunity

Proteins can be valuable therapeutic drugs, but they often cause immune reactions. The gold-standard strategy to diminish those negative effects is to coat proteins with polyethylene glycol (PEG) chains. For many patients, however, the immune system still reacts to form anti-PEG antibodies, which can lead to diminished drug efficacy and allergic reactions. University of Washington, Seattle, researchers led by Shaoyi Jiang have therefore turned to polycarboxybetaine (PCB) as an alternative (Proc. Natl. Acad. Sci. USA 2015, DOI: 10.1073/pnas.1512465112). PCB is made from a zwitterionic monomer (carboxybetaine acrylamide), which results in a zwitterionic polymer that is more hydrophilic and thus more biocompatible than PEG. Jiang’s team created a cross-linked PCB network that more completely covers and protects the surface of therapeutic proteins from recognition by the immune system. The researchers tested their new approach on uricase, an enzyme biotherapy for gout. And although native uricase triggered high levels of antibodies in healthy rats, rats treated with PCB-coated uricase produced no anti-uricase or anti-PCB antibodies. Jiang anticipates PCB or other zwitterionic materials may open up possibilities for biomolecules previously assumed to be too immunogenic for therapeutic use.