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PhD Defence: Quantification of therepeutic antibodies and endogenous proteins with LC-MS/MS

Therapeutic monoclonal antibodies are widely used for the treatment of various diseases were conventional small molecule based drugs are not effective. For patients with inflammatory autoimmune disease for example, the overproduction of TNF-alpha protein causes painful inflammatory symptoms. The level of TNF-alpha can be reduced through treatment with therapeutic monoclonal antibodies such as infliximab or adalimumab. However, some patients develop anti-drug antibodies that target these therapeutic ‘exogenous’ proteins thus reducing the drug concentration in plasma. This in turn renders the treatment ineffective. In this case quantitative proteomics is used for therapeutic drug monitoring of drug concentration in plasma. This provides the clinician useful insight to what is happening in the patient’s body and can be used to tailor the patient’s care.


Quantitative proteomics can also be used for endogenous proteins. Endogenous proteins are synthesized by the DNA within the cell nucleus. Endogenous proteins are the building blocks for all cells that make up the organism, they play a role in food digestion, they offer protection from pathogens and they heal the cells when damaged. The ability to determine whether these proteins are present in the required concentration in plasma can help the clinician to diagnose a disease but also to personalize the treatment plan.


This thesis provides a tutorial for quantitative proteomics with liquid chromatography-tandem mass spectrometry (LC-MS/MS), furthermore various examples of bioanalytical quantification of endogenous and therapeutic proteins in human plasma are presented. Novel sample purification strategies are introduced and optimized though experimental design.

Start date and time
End date and time
Location
University Hall
PhD candidate
Mo el Amrani
Dissertation
Quantification of therepeutic antibodies and endogenous proteins with LC-MS/MS
PhD supervisor(s)
Prof. A.D.R. Huitema
Prof. C.E. Hack
Co-supervisor(s)
dr. E.M. van Maarseveen
Entrance fee
Free
Registration

Not necessary