Oxidation, aggregation and immunogenicity of therapeutic proteins

Torosantucci, R. (2013)

Doctoral Thesis

The aim of the research described in this thesis is to study the chemical mechanisms responsible for protein aggregation induced by metal catalyzed oxidation and to investigate the relationship between protein oxidation, aggregation and immunogenicity. To this end, recombinant human insulin rhIFN_-1a and rhIFN_-2a are used in conjunction with transgenic mice immune tolerant for the respective human endogenous counterparts. The impact of PEGylation on aggregate formation and excipients to prevent metal catalyzed oxidation are also evaluated.

• Metal catalyzed oxidation
• Mass spectrometry
• DOPA
• Immunogenicity
• PEGylation
• Anti-oxidant
• Therapeutic proteins

• All authors: Torosantucci, R.
• Supervisor: Jiskoot, W.; Schellekens, H.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Science, Leiden University
• Date: 2013-09-17
• ISBN (print): 9789461084835
• Sponsorship: Merck & Co.