Stefan Ståhl
Department of Molecular Biotechnology, School of Biotechnology, Royal Institute of Technology (KTH), AlbaNova University Center, Stockholm, Sweden

Abstract:

Affibody molecules constitute a class of engineered affinity proteins with proven potential for therapeutic, diagnostic and biotechnological applications. Affibody molecules are small (6.5 kDa) single domain proteins that can be isolated for high affinity and specificity to given protein targets. Fifteen years after its discovery, the affibody technology is gaining use in many groups as a tool for creating molecular specificity wherever a small, engineering compatible tool is warranted. The generation and use of affibody molecules binding with high affinity to the human epidermal growth factor receptors, EFGR, HER2 and HER3 and their use for medical imaging applications as well as tumor therapy will be addressed. High contrast gamma camera images in mouse xenografts as well as data on complete eradication of small HER2-expressing tumors in mice will be shown. The first human study for affibody-mediated imaging of HER2-expressing metastatic lesions in recurrent breast cancer will be presented.

In addition, an affibody molecule specific for the amyloid-β (Aβ) peptide involved in Alzheimer’s disease was recently generated. The structure of the affibody molecule in complex with Aβ was solved by NMR, revealing that two affibody molecules dimerize upon binding the peptide. Interestingly, both affibody molecules and the Aβ peptide undergo structure reorganization upon binding, resulting in a barrel formation of the two affibody molecules, capturing the Aβ peptide. By burying the hydrophobic parts of the aggregation-prone Aβ peptide, the affibody molecule inhibits amyloid fibrillation. Furthermore, it was recently demonstratedthe same Aβ–specific affibody molecule, expressed in the brain of a Drosophila melanogaster model of Alzheimer’s disease, eliminated neurotoxicity by increasing the clearance of Aβ from the brain.