1. Different antitumor activities of anti-bFGF neutralizing antibodies: heparin-binding domain provides an inefficient epitope for neutralization in vivo.
- Author
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Aonuma M, Yoshitake Y, Nishikawa K, and Tanaka NG
- Subjects
- Animals, Antibodies, Monoclonal metabolism, Binding Sites, Antibody, Cell Division drug effects, Colorectal Neoplasms immunology, Colorectal Neoplasms metabolism, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Epitopes immunology, Female, Fibroblast Growth Factor 2 pharmacology, Fibroblast Growth Factor 2 physiology, Heparin immunology, Humans, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Protein Structure, Tertiary, Recombinant Proteins immunology, Recombinant Proteins metabolism, Time Factors, Tumor Cells, Cultured, Antibodies, Monoclonal pharmacology, Epitopes metabolism, Fibroblast Growth Factor 2 immunology, Heparin metabolism
- 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.
- Published
- 1999