Targeting by affinity-matured recombinant antibody fragments of an angiogenesis associated fibronectin isoform.
The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition of this isoform. We describe the use of these fragments in nude mice to target an aggressive tumor (grafted F9 murine teratocarcinoma). Imaging in real time was done by infrared photodetection of a chemically coupled fluorophore. The targeting was improved by use of affinity-matured fragments with low kinetic dissociation rates (koff = 1.5 x 10(-4) s-1) and also by engineering dimeric fragments via a C-terminal amphipathic helix.
Neri
D
D
Cambridge Centre for Protein Engineering-MRC Centre, UK.
Carnemolla
B
B
Nissim
A
A
Leprini
A
A
Querzè
G
G
Balza
E
E
Pini
A
A
Tarli
L
L
Halin
C
C
Neri
P
P
Zardi
L
L
Winter
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007128:Immunoglobulin Fragments / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D011994:Recombinant Proteins / Q000378:metabolism; D018243:Teratocarcinoma / Q000098:blood supply / Q000175:diagnosis
D017931:DNA Primers; D005353:Fibronectins; D007128:Immunoglobulin Fragments; D011994:Recombinant Proteins