Germline humanization of a murine Aβ antibody and crystal structure of the humanized recombinant Fab fragment
Citations Over Time
Abstract
Alzheimer's disease is the most common form of dementia, affecting 26 million people worldwide. The Abeta peptide (39-43 amino acids) derived from the proteolytic cleavage of the amyloid precursor protein is one of the main constituents of amyloid plaques associated with disease pathogenesis and therefore a validated target for therapy. Recently, we characterized antibody fragments (Fab and scFvs) derived from the murine monoclonal antibody WO-2, which bind the immunodominant epitope ((3)EFRH(6)) in the Abeta peptide at the N-terminus. In vitro, these fragments are able to inhibit fibril formation, disaggregate preformed amyloid fibrils, and protect neuroblastoma cells against oligomer-mediated toxicity. In this study, we describe the humanization of WO-2 using complementary determining region loop grafting onto the human germline gene and the determination of the three-dimensional structure by X-ray crystallography. This humanized version retains a high affinity for the Abeta peptide and therefore is a potential candidate for passive immunotherapy of Alzheimer's disease.
Related Papers
- → Dissecting Linear and Conformational Epitopes on the Native Thyrotropin Receptor(2004)40 cited
- → Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes(2000)68 cited
- → Fine-structure epitope mapping of antierythropoietin monoclonal antibodies reveals a model of recombinant human erythropoietin structure(1996)38 cited
- → A Linear Region of a Monoclonal Antibody Conformational Epitope Mapped on p185HER2 Oncoprotein(1997)15 cited
- Research Progress in Conformational Epitope Mapping Approaches for Food Allergens(2012)