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BSG antibodies have transendothelial cell drug delivery capability

Time：

2022-06-21

　　The blood-brain barrier (BBB) poses a challenge to antibody-based brain therapies and is a major barrier to the successful application of biotherapeutics in the treatment of brain diseases. Since only a small fraction of monoclonal antibodies (mAbs) are able to penetrate the blood-brain barrier, large doses of therapeutic agents are required to elicit drug effects. This limitation has triggered studies to improve blood-brain barrier transport through receptor-mediated intracellular phagocytosis, and several receptors have been explored to mediate this process. One recently proposed candidate gene is the expression of basic proteins by brain endothelial cells (BECs).

　　Scientists explored the intracellular function of different basigin monoclonal antibodies targeting different epitopes using a porcine in vitro blood-brain barrier model and provided data showing the classification of intracellular vesicles of these basigin monoclonal antibodies in porcine BECs. These data suggest that basigin monoclonal antibodies avoid the lysosomal degradation pathway and internalize into vesicles that are used by circulating receptors. In an in vitro BBB co-culture model, contact of basigin monoclonal antibodies with basigin monoclonal antibodies resulted in transfer of monoclonal antibodies into astrocytes via tightly packed BECs. Although monoclonal antibodies with higher binding affinity for basigin showed greater astrocyte internalization, it is unclear whether this cytokinesis is affinity- or epitope-dependent, or a combination of both, based on the scientists' experiments.

　　In conclusion, this study provides information on the intracellular and intercellular fate of basigin monoclonal antibodies in BECs, which could be valuable for the future design of basigin-mediated drug delivery platforms.

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