"A fusion protein consisting of a single-chain Fv directed against secretory component, the extracellular portion of the pIgR, linked to human 1-antitrypsin is effectively ferried across human tracheal xenografts and delivers the antiprotease to the apical surface to a much greater extent than occurs by passive diffusion of human 1-antitrypsin alone... Aerosolization of antiproteases, like human 1-antitrypsin (hA1AT), should permit direct delivery to the airways, but delivery to a diseased lung by this route is uneven and favors less diseased sites. Moreover, the drug is deposited atop the mucus blanket rather than the critical site at the surface of the cell (13). Systemic administration of hA1AT (14) for CF is inefficient because the airway epithelium is relatively impermeable to macromolecules, thereby preventing their diffusion across by the junctional complexes that connect adjacent epithelial cells (15)...We developed a novel strategy to circumvent these difficulties and protect the respiratory epithelial cell surface directly by exploiting properties of the pIgR. The human pIgR (hpIgR) is expressed at high levels in the airway epithelium and serous cells of the submucosal glands and is specifically adapted for the uptake and nondegradative transfer of polymeric antibodies to the lumenal surface of epithelia. We have shown previously that fusion proteins containing a single-chain Fv (scFv) antibody directed at the extracellular domain of hpIgR or human secretory component (hSC), linked to hA1AT, can be transported vectorially from the basolateral surface of cultured epithelial cells to the immediate surface where it can potentially have the greatest impact on endobronchial inflammation by blocking free proteases (16, 17). Moreover, the Fv-based fusion protein secreted in the ASF was fully active as an antiprotease..." http://ajrccm.atsjournals.org/cgi/content/full/167/10/1374
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