Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 42, Pages 13873-13876Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201808615
Keywords
antibodies; immunochemistry; polymers; protein modifications; zwitterions
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Funding
- Defense Threat Reduction Agency [HDTRA1-13-1-0044]
- University of Washington
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Poly(ethylene glycol) (PEG) conjugation has been the gold standard to ameliorate the pharmacokinetic (PK) and immunological profiles of proteins. PEG polymer does become immunogenic once attached to proteins, evoking PEG-specific antibody (Ab) responses. The anti-PEG Abs could cause PEGylated biologic treatments to fail and even result in lethal adverse reactions. Thus the zwitterionic poly(carboxybetaine) (PCB) has been introduced as a PEG substitute for protein modification. Addressed herein is anti-polymer Ab induction by conjugating PEG and PCB polymers to a series of carrier proteins with escalating immunogenicity. Results indicate that titers of PEG-specific Abs were quantitatively correlated to the immunogenicity of carrier proteins, whereas the generation of PCB-specific Abs was minimal and insensitive to increased protein immunogenicity. This work provides insight into the immunological properties of PEG and PCB and has far-reaching implications for the development of polymer-protein conjugates.
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