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 (scFvs) 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 pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8x10(-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.
Tao
Jun
J
Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
Xiang
Jun-Jian
JJ
Li
Dan
D
Deng
Ning
N
Wang
Hong
H
Gong
Yi-Ping
YP
D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000276:immunology*; D009369:Neoplasms / Q000378:metabolism*
D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D007135:Immunoglobulin Variable Region; D016222:Fibroblast Growth Factor 2