AbstractWe aim to design a good, robust and generic tool to extend the half-life of molecules. Therefore, we investigate a recently identified serum albumin targeting Nanobody (SA 1 clone). A Nanobody is considered, in general, as the smallest intact antigen-binding domain (15 kDna), derived from heavy chain only antibodies (HCAb) and it seems like a perfect instrument for this purpose. Nanobodies can be conjugated or co-expressed at their N- or C-terminal region with a tracer or molecule exhibiting therapeutic activity. In our study, we used 2Rs15d as a tracer, which is a Nanobody capable of targeting tumors expressing the HER2 receptor. Recently positive preclinical tests performed on mice have verified the targeting ability of this tracer when labeled with 99mTc isotope, allowing the nanobody to proceed to the next experimental phase in the clinic.
In this thesis we have proven the ability of serum albumin targeting Nanobody to increase serum half-life of a 2Rs15d, without decreasing its targeting potential. We have also shown the effect of size on blood clearance by investigating bivalent and monovalent Nanobodies. Finally we have confirmed the blocking potential of a bi-specific serum half-life extended Nanobody which is targeting the receptor epitope of HER2.
|Date of Award||Sep 2013|
|Supervisor||Serge Muyldermans (Promotor), Gholamreza Hassanzadeh Ghassabeh (Co-promotor), Nick Devoogdt (Co-promotor) & Vicky Caveliers (Jury)|
- Serum albumin