Couch Blood-Brain Barrier Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the

when using TfR as a molecular lift. discoveries suggest that the blood-brain barrier is not the only obstacle to surmount on the way to the brain, at least loss of these cells may be less likely to occur in primates than in mice. The translational implications of these minimal sustained toxicity. Investigation of monkey and human TfR levels in circulating reticulocytes suggested that , a toxic protein implicated in Alzheimer's disease, with β doses of TfR/BACE1 bispecific antibodies reduced amyloidantibodies were administered to mice, despite the high expression of TfR in brain endothelial cells. Finally, multiple investigated. The authors observed, for example, that the blood-brain barrier remained completely intact after TfR Because reticulocytes express high levels of TfR, other cell types that express high levels of TfR were also extent of reticulocyte loss was also influenced by binding to TfR and interaction with the complement cascade. lack Fc interactions with immune cells eliminated adverse acute clinical reactions and reduced reticulocyte loss; the reactions and a reduction in immature red blood cells, known as reticulocytes. TfR bispecific antibodies engineered to colleagues now report that when mice were dosed with therapeutic TfR antibodies, the animals showed acute clinical , Couch and Science Translational Medicine ramifications of this approach. Building on a pair of studies published in into the brain. Although TfR can act as a molecular lift to promote brain uptake, little is known about the safety uptake Bispecific antibodies using the transferrin receptor (TfR) have shown promise for boosting therapeutic antibody The blood-brain barrier represents a formidable blockade preventing therapeutic antibody delivery into the brain. Averting Roadblocks En Route to the Brain