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Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target.
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ID: paper-21613623
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Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target.
["Yu Y", "Zhang Y", "Kenrick M", "Hoyte K", "Luk W", "Lu Y", "Atwal J", "Elliott J", "Prabhu S", "Watts R"]
Abstract
Monoclonal antibodies have therapeutic potential for treating diseases of the central nervous system, but their accumulation in the brain is limited by the blood-brain barrier (BBB). Here, we show that reducing the affinity of an antibody for the transferrin receptor (TfR) enhances receptor-mediated transcytosis of the anti-TfR antibody across the BBB into the mouse brain where it reaches therapeutically relevant concentrations. Anti-TfR antibodies that bind with high affinity to TfR remain asso...
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