Proactively Reducing Anti‐Drug Antibodies via Immunomodulatory Bioconjugation
Abstract
Although PEGylation reduces the immunogenicity of protein drugs to some extent, its limitations for highly immunogenic biotherapeutics have been demonstrated. Herein, a proactive strategy to alleviate the development of anti‐drug antibodies (ADAs) against protein drugs by immunomodulatory bioconjugation is reported. Rapamycin was conjugated to a PEGylated protein therapeutic via a cleavable disulfide linker. The conjugated rapamycin can be released from the bioconjugate and prevent immune responses once the bioconjugate is uptaken by antigen‐presenting cells. The immunomodulatory bioconjugate significantly reduced the titers of ADAs compared with a PEGylated protein. The inhibition of immune responses was specific to the conjugated antigen, avoiding systemic immune suppression and the risk of increased susceptibility to infections. The reported approach breaks the limitations of PEGylation by the proactive prevention of ADAs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 24, 2019
- Source ID
- 10.1002/ange.201814275
Entities
People
- Caroline Tsao
- Kan Wu
- Peng Zhang
- Priyesh Jain
- Shaoyi Jiang
Organizations
- Defense Threat Reduction Agency
- University of Washington