1 research outputs found
Inhibitor-Decorated Polymer Conjugates Targeting Fibroblast Activation Protein
Proteases
are directly involved in cancer pathogenesis. Expression
of fibroblast activation protein (FAP) is upregulated in stromal fibroblasts
in more than 90% of epithelial cancers and is associated with tumor
progression. FAP expression is minimal or absent in most normal adult
tissues, suggesting its promise as a target for the diagnosis or treatment
of various cancers. Here, we report preparation of a polymer conjugate
(an iBody) containing a FAP-specific inhibitor as the targeting ligand.
The iBody inhibits both human and mouse FAP with low nanomolar inhibition
constants but does not inhibit close FAP homologues dipeptidyl peptidase
IV, dipeptidyl peptidase 9, and prolyl oligopeptidase. We demonstrate
the applicability of this iBody for the isolation of FAP from cell
lysates and blood serum as well as for its detection by ELISA, Western
blot, flow cytometry, and confocal microscopy. Our results show the
iBody is a useful tool for FAP targeting in vitro and potentially
also for specific anticancer drug delivery