PEGylation and anti-PEG antibodies

Abstract

Polyethylene glycol (PEG) is generally considered a stealth polymer that is universally used to extend the circulation times and enhance the therapeutic efficacy of nanocarrier-based and/or protein therapeutics. Nonetheless, in contrast to the general concept that PEG is nonimmunogenic, a growing body of literature has emerged declaring PEG to be immunogenic, which is manifested by the robust production of anti-PEG antibodies. The existence of such anti-PEG antibodies has been intimately correlated with an impairment of therapeutic efficacy in tandem with the development of severe adverse effects in several clinical settings employing PEGylated-based therapeutics. This chapter is a discussion of the mechanisms beyond anti-PEG immunity as well as the implications that preexisting and treatment-induced anti-PEG antibodies is exerting on the fate of PEGylated products. In addition, several alternative technologies beyond PEGylation are highlighted.