title: Different antitumor activities of anti-bFGF neutralizing antibodies: heparin-binding domain provides an inefficient epitope for neutralization in vivo.
abstract: Basic fibroblast growth factor (bFGF) plays an important role in tumor growth and angiogenesis. To elucidate the efficient recognition sites by anti-bFGF neutralizing antibodies, we generated two anti-bFGF neutralizing monoclonal IgG1 antibodies (mAbs), 2G11 and 1E6, recognizing different sites, and estimated as binding to the heparin-binding and the receptor-binding regions of bFGF, respectively, both of which have been shown to be important for its receptor interaction. Despite their high in vitro anti-bFGF activity in the absence of heparin, 2G11, with in vitro activity in competition with heparin, failed to inhibit the in vivo tumor growth of bFGF-producing RPMI4788 cells, though 1E6, showing non-competition with heparin, exhibited a significant antitumor effect. These results show that the heparin-binding domain of bFGF provides an inefficient epitope for in vivo neutralization of anti-bFGF mAb, and anti-bFGF neutralizing mAbs without competition against heparin have the potential to show in vivo antitumor effects.
authors.affiliation: New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Aonuma
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: N G
authors.initials: NG
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000276:immunology* / Q000494:pharmacology / Q000502:physiology; D006493:Heparin / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D006493:Heparin