TY - JOUR
T1 - Preparation of phage antibodies to the ED-A domain of human fibronectin
AU - Borsi, Laura
AU - Castellani, Patrizia
AU - Allemanni, Giorgio
AU - Neri, Dario
AU - Zardi, Luciano
PY - 1998/5/1
Y1 - 1998/5/1
N2 - The fibronectin (FN) isoform containing the alternative spliced ED-A domain is much more expressed in fetal, tumoral, and regenerating tissues than in normal adult tissues. The ED-A containing FN is up-regulated by numerous cytokines, such as TGF-β, and, although in normal adult liver the ED-A domain is undetectable, in regenerating rat liver the expression of ED- A is increased and mediates the conversion of fat storing cells to myofibroblasts. Here we describe the selection from a phage display library and the characterization of human antibody fragments directed against the EDA sequence of FN. As they can be easily radiolabeled with 32P, these antibodies are very highly sensitive reagents for the determination of ED-A levels in tissues and biological fluids; in fact, use of these scFv induced a more than 10-fold increase in sensitivity with respect to the murine monoclonal IST-9. The possibility of preparing a range of human engineered antibodies should facilitate the development of antibody reagents with suitable pharmacokinetics, valency, functional affinity, and effector functions and that could be useful for clinical purposes.
AB - The fibronectin (FN) isoform containing the alternative spliced ED-A domain is much more expressed in fetal, tumoral, and regenerating tissues than in normal adult tissues. The ED-A containing FN is up-regulated by numerous cytokines, such as TGF-β, and, although in normal adult liver the ED-A domain is undetectable, in regenerating rat liver the expression of ED- A is increased and mediates the conversion of fat storing cells to myofibroblasts. Here we describe the selection from a phage display library and the characterization of human antibody fragments directed against the EDA sequence of FN. As they can be easily radiolabeled with 32P, these antibodies are very highly sensitive reagents for the determination of ED-A levels in tissues and biological fluids; in fact, use of these scFv induced a more than 10-fold increase in sensitivity with respect to the murine monoclonal IST-9. The possibility of preparing a range of human engineered antibodies should facilitate the development of antibody reagents with suitable pharmacokinetics, valency, functional affinity, and effector functions and that could be useful for clinical purposes.
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U2 - 10.1006/excr.1998.3946
DO - 10.1006/excr.1998.3946
M3 - Article
C2 - 9596997
AN - SCOPUS:0031826661
VL - 240
SP - 244
EP - 251
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -