Therapeutic proteins revolutionized the treatment of many, often severe diseases. However, their use is associated with the risk of unwanted immune responses. Anti‐drug antibodies (ADA) can decrease the treatment’s efficacy, completely block the activity of drug, or even cross‐react with endogenous protein leading to severe, potentially life‐threatening side effects. Introduction of recombinant human (rh) protein therapeutics onto the market was expected to overcome the immunogenicity problem. Unfortunately, rh proteins still induce ADA in at least part of the patients. Although many factors have been correlated with increased risk of immunogenicity the presence of protein aggregates in formulated product seems to be the most crucial

1. Protein aggregates are defined as assemblies of protein molecules other than the intended(functional) species. Thus, for monoclonal antibodies even a dimer is classified as an aggregate. In fact dimers are one of the most commonly found impurities of protein products. Lacking is, however, knowledge about their impact on the immunogenicity of protein drugs. It has been shown that depending on stress conditions morphologically different dimers are formed

2. Possibly such dimers are not equally immunogenic.

Aims of the project: The goal of the study project is to determine the potential immunogenicity of different dimers in a mouse model.

Student will be responsible for:
‐ Development of dimerization protocols
‐ Characterization of isolated dimer samples (structural analysis, potency, stability, etc.)
‐ Preparation of samples for animal experiment
‐ Detection of immune response triggered by dimers

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