TARGETING BY AFFINITY-MATURED RECOMBINANT ANTIBODY FRAGMENTS OF AN ANGIOGENESIS ASSOCIATED FIBRONECTIN ISOFORM

The oncofetal fibronectin (B-FN) isoform is present in vessels of neop lastic tissues during angiogenesis but not in mature vessels, B-FN cou ld therefore provide a target for diagnostic imaging and therapy of ca ncer, Phage display libraries have been used to isolate human antibody fragments with pan-species recognition of this isoform, We describe t he use of these fragments in nude mice to target an aggressive tumor ( grafted Fg murine teratocarcinoma). Imaging in real time was done by i nfrared photodetection of a chemically coupled fluorophore, The target ing was improved by use of affinity-matured fragments with law kinetic dissociation rates (k(off)=1.5x10(-4) s(-1)) and also by engineering dimeric fragments via a C-terminal amphipathic helix.