Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (says) that bind to human FGF-2 After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor This 1A2 scFv was then cloned into the plgG1 vector and expressed in 293T cells The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10(-9) M to rhFGF-2 In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival (C) 2010 Elsevier Inc All rights reserved