Up-regulated basic fibroblast growth factor (bFGF or FGF-2) plays an important role in the development and metastasis of melanoma; therefore, neutralizing antibodies to bFGF may suppress melanoma growth. In this study, we have developed three monoclonal antibodies against bFGF (anti-bFGF mAbs), which display remarkable anti-tumor and anti-angiogenic effects in vitro and in vivo. Anti-bFGF mAbs significantly inhibit the proliferation and induce apoptosis of B16 cells, and show inhibitory effects on the migration of B16F10 cells and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Treatment of B16 melanoma spheroids with anti-bFGF mAbs in vivo results in significant reduction in tumor size and prolonged survival time of animals. Moreover, TUNEL (terminal transferase dUTP nick end labeling) assay and CD31 staining confirmed the increase of apoptosis and decrease of intratumoral microvessel density in tumor sections from animals treated with anti-bFGF mAbs. Our data indicate that anti-bFGF mAbs are potential therapeutic candidates for melanoma therapy by effectively suppressing the melanoma growth through inhibition of angiogenesis and induction of apoptosis in the tumor.
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Monoclonal antibodies targeting basic fibroblast growth factor inhibit the growth of B16 melanoma in vivo and in vitro.
Oncol Rep
August 2010
Department of Immunology, Southern Medical University, Guangzhou 510515, PR China.
Up-regulated basic fibroblast growth factor (bFGF or FGF-2) plays an important role in the development and metastasis of melanoma; therefore, neutralizing antibodies to bFGF may suppress melanoma growth. In this study, we have developed three monoclonal antibodies against bFGF (anti-bFGF mAbs), which display remarkable anti-tumor and anti-angiogenic effects in vitro and in vivo. Anti-bFGF mAbs significantly inhibit the proliferation and induce apoptosis of B16 cells, and show inhibitory effects on the migration of B16F10 cells and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro.
View Article and Find Full Text PDF[Cloning of the variable region genes from hybridoma against bFGF and expression of single chain antibody fragments in E.coli HB2151].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
December 2007
Center of Antibody Engineering, Jinan University, Guangzhou 510632, China.
Aim: To construct and express the single chain antibody (scFv) in E.coli HB2151 by cloning the variable region genes from hybridoma against bFGF.
Methods: Total RNA was extracted from hybridoma cell line B2F3 secreting mAbs against bFGF and the cDNA was amplified by retropolymerase chain reaction (RT-PCR).
Different antitumor activities of anti-bFGF neutralizing antibodies: heparin-binding domain provides an inefficient epitope for neutralization in vivo.
Anticancer Res
February 2000
New Product Research Laboratories IV, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
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.
View Article and Find Full Text PDFIdentification of a monoclonal antibody, TV-1, directed against the basement membrane of tumor vessels, and its use to enhance the delivery of macromolecules to tumors after conjugation with interleukin 2.
Cancer Res
June 1995
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
mAbs reactive with epitopes expressed on tumor vessels were evaluated as universal delivery agents of peptides with vasoactive properties to enhance the uptake of macromolecules in tumors. Unlike other reported approaches to target tumor vessels, a mAb designated TV-1 targets a basement membrane antigen that is found in all tissues but that is accessible only in tumor vessels, making it an alternative vehicle for the delivery of biologically active peptides to tumors. A panel of 30 monoclonal and polyclonal antibodies was screened by immunohistochemistry on sections of human tumors, normal vascular endothelium, and connective tissues.
View Article and Find Full Text PDFFluorometric enzyme immunoassay of basic fibroblast growth factor with monoclonal antibodies.
Clin Chem
October 1992
Gifu Pharmaceutical University, Department of Molecular Biology, Japan.
We compared three different strategies for measuring basic fibroblast growth factor (bFGF) by fluorometric enzyme immunoassay (EIA). After optimizing conditions, we found that a primary anti-bFGF MAb directly conjugated with peroxidase gave the best detection limit for recombinant bFGF (approximately 30 ng/L, 3 pg/assay tube) in a two-site sandwich assay. The detection limit of methods based on biotinylated primary MAbs or on secondary antibodies followed by streptavidin-conjugated peroxidase was slightly lower than that of the above method.
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