Monoclonal antibodies directed against basic fibroblast growth factor which inhibit its biological activity in vitro and in vivo.
A panel of four murine monoclonal IgG1 antibodies (mAbs) to a recombinant form of basic fibroblast growth factor (bFGF) was produced using somatic cell fusion techniques. Non-linear regression analysis of radioimmunoassay data for each mAb yielded the following dissociation constants (nM) for their interactions with bFGF: DE6 (0.822); AF11 (2.0); FE8 (2.31); and DG2 (20.0). One of the mAbs, DG2, was identified as a bFGF neutralizing antibody on the basis of its ability to inhibit, in vitro, the binding of [125I]-bFGF to high and low affinity bFGF sites on cultured baby hamster kidney cells and bFGF-induced [3H]-thymidine incorporation in cultured 3T3 cells, and in vivo, the angiogenic response to bFGF in a rat kidney capsule model of angiogenesis. The other mAbs displayed varying inhibitory activities in these assays. These mAbs, particularly DG2, may be well suited for a number of applications in bFGF research including immunoassays, immunohistochemical studies, and as functional antagonists of bFGF for examining its role in physiological processes such as reproduction, growth, and development.
Reilly
T M
TM
E.I. du Pont de Nemours and Company, Inc. Medical Products Department, Wilmington, Delaware 19880-0400.
Taylor
D S
DS
Herblin
W F
WF
Thoolen
M J
MJ
Chiu
A T
AT
Watson
D W
DW
Timmermans
P B
PB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009389:Neovascularization, Pathologic; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors