Work

Proactively Reducing Anti‐Drug Antibodies via Immunomodulatory Bioconjugation

Year: 2019

Type: article

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.

Source: Angewandte Chemie

DOI: 10.1002/ange.201814275

Authors: Peng Zhang, Priyesh Jain, Caroline Tsao, Kan Wu, Shaoyi Jiang

Institution: University of Washington

Language: English

Topic: Monoclonal and Polyclonal Antibodies Research

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: University of Washington, Defense Threat Reduction Agency