Zwitterionic Nanocages Overcome the Efficacy Loss of Biologic Drugs
Abstract
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinicalâmimicking gouty rat model to determine any loss of efficacy evoked after five administrations.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 19, 2018
- Source ID
- 10.1002/adma.201705728
Entities
People
- Andrew Sinclair
- Bowen Li
- Caroline Tsao
- Hsiangâchieh Hung
- Jingyi Xie
- Kan Wu
- Peng Zhang
- Priyesh Jain
- Shaoyi Jiang
- Tao Bai
- Xiaojie Lin
- Zhefan Yuan
Organizations
- Defense Threat Reduction Agency
- National Institutes of Health
- University of Washington