Fusion of an albumin-binding domain extends the half-life of immunotoxins.

摘要: Immunotoxins have documented potential as a cancer treatment due to their extreme potency; single toxin molecule delivered the cytosol may be sufficient kill cell. However, short half-life in circulatory system one of key problems associated with clinical use immunotoxins and continue limit therapeutic activity. Herein, we genetically fused an albumin-binding domain (ABD) human epidermal growth factor receptor 2 (HER2)-specific immunotoxin ZHER2-PE38 extend circulation time thus improve outcome this immunotoxin. Furthermore, fusion ABD was found promote non-covalent interactions between serum albumin, which rescue from lysosomal degradation through albumin-mediated interaction neonatal Fc (FcRn). This manuscript reports construction, purification, characterization ABD-fused HER2-specific immunotoxin, ABD-ZHER2-PE38, both vitro vivo. Compared non-fused ZHER2-PE38, new construct exhibits clearly increased plasma (330.8 versus 13.5min, approximately 24.4-fold extension) remarkably improved antitumor effects NCI-N87 subcutaneous xenograft model. Therefore, represents potentially attractive modality, proposed strategy also useful applications for current designs.