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Brain Shuttle Antibody for Alzheimer's Disease with Attenuated Peripheral Effector Function due to an Inverted Binding Mode.

Cell Rep. 2018; 
Weber Felix,Bohrmann Bernd,Niewoehner Jens,Fischer Jens A A,Rueger Petra,Tiefenthaler Georg,Moelleken Joerg,Bujotzek Alexander,Brady Kevin,Singer Thomas,Ebeling Martin,Iglesias Antonio,Freskg?rd Per
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Recombinant Proteins factor (GenScript Z02001). We used differentiated human macrophages cultured in RPMI 1640 (Gibco Get A Quote


Receptors show promise for the transport of monoclonal antibodies (mAbs) across the blood-brain barrier. However, safety liabilities associated with peripheral receptor binding and Fc effector function have been reported. We present the Brain Shuttle-mAb (BS-mAb) technology, and we investigate the role of Fc effector function in?vitro and in an Fcγ receptor (FcγR)-humanized mouse model. Strong first infusion reactions (FIRs) were observed for a conventional mAb against transferrin receptor (TfR) with a wild-type immunoglobulin G1 (IgG1) Fc. Fc effector-dead constructs completely eliminated all FIRs. Remarkably, no FIR was observed for the BS-mAb construct with a native IgG1 Fc function. Using various BS... More


Alzheimer’s disease,Brain Shuttle,antibody effector function,antibody engineering,blood-brain barrier,brain deli