Digital Public Defence: Simone Mester
MSc Simone Mester at Institute of Clinical Medicine will be defending the thesis “IgA-based antibody formats with extended plasma half-life and potent effector functions” for the degree of PhD (Philosophiae Doctor).
Photo: Ine Eriksen, UiO
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
- First opponent: Professor Mark Cragg, University of Southampton, UK
- Second opponent: Senior Scientist Anette Weyergang, Oslo University Hospital
- Third member and chair of the evaluation committee: Senior Scientist Espen Melum, University of Oslo
Chair of the Defence
Professor Frode Lars Jahnsen, University of Oslo
Professor Jan Terje Andersen, University of Oslo
Antibodies are key players of the immune system, that link recognition of a target with elimination mechanisms after engagement of immune cells and activation of the complement system. Antibodies are also important as therapeutics and have revolutionized treatment of an increasing number of diseases, including cancer. Current therapeutic antibodies are based on the IgG isotype. Due to their clinical success, there is a continuous interest in design of new formats that are further tailored for specific use.
In this regard, IgA has emerged as a promising isotype for treatment of cancer, based on its ability to efficiently recruit myeloid cells, and in particular neutrophils that express the IgA receptor which can induce efficient target cell killing. However, no IgA-based product has yet reached the clinical pipeline. One reason for this is its naturally short plasma half-life of less than a week in humans, that may hamper the therapeutic effect.
To overcome this limitation, Simone Mester and colleagues explore different half-life extension strategies for human IgA by taking advantage of knowledge of IgG and albumin biology. These unrelated proteins engage the neonatal Fc receptor (FcRn), which acts as a regulator of their 3-week long half-life in humans. Specifically, FcRn binding rescues both ligands from intracellular degradation through a pH-dependent intracellular recycling mechanism.
The thesis describes new strategies to extend the plasma half-life of IgA by targeting of FcRn. The work should inspire development of antibody-based therapeutic candidates with tailored plasma half-life combined with potent tumor killing properties.
Contact the research support staff.