Polymer reduces drug conjugate immunogenicity

An analog of polyethylene glycol (PEG) causes fewer immune reactions than PEG. PEG conjugation has been widely used to increase the longevity of drug action and protect drug molecules from being attacked by the immune system. However, prior exposure to PEG from its widespread use in consumer products, foods, and drugs has caused many people to develop immune reactions to the polymer itself, potentially reducing the efficacy of PEG­ylated drugs and causing unwanted side effects. To address this problem, Ashutosh Chilkoti of Duke University and coworkers developed a brush polymer called POEGMA, poly[oligo(ethylene glycol) methyl ether methacrylate], as a PEG substitute (Nat. Biomed. Eng. 2016, DOI: 10.1038/s41551-016-0002). They used a technique called in situ atom transfer radical polymerization to conjugate POEGMAs having different numbers of ethylene glycol side chains to exendin-4, a therapeutic peptide used clinically to treat type 2 diabetes. The conjugates reduced or eliminated immune interactions with preexisting PEG antibodies in patient plasma samples compared with those of two FDA-approved PEG­ylated protein drugs. And the conjugates didn’t reduce drug efficacy, as tested in mice. The findings suggest that POEGMA may be an attractive next-generation replacement for PEG­ylation of peptide and protein drugs.