Effect of intraperitoneally, intravenously and intralesionally administered monoclonal anti-beta-FGF antibodies on rat chondrosarcoma tumor vascularization and growth.
The growth and vascularization of many tumours has been reported to be associated with the overexpression of the potent mitogenic and angiogenic polypeptide basic fibroblast growth factor (beta-FGF). Consequently, it has been proposed that inhibition of beta-FGF action would prevent the growth of beta-FGF-dependent tumours. In this study, cell culture assays were established to assess the ability of mouse monoclonal DG-2 anti-beta-FGF antibodies to inhibit the mitogenic action of beta-FGF in vitro. Following in vitro characterisation, the monoclonal DG-2 antibodies were used to evaluate the role of beta-FGF in promoting the vascularization and growth of rat chondrosarcoma tumours. The effect the monoclonal anti-B-FGF antibodies had on tumour vascularization and growth in vivo were monitored using a 99m Technetium (99mTc)-labelled red blood cell procedure. The characterization studies confirmed that the DG-2 monoclonal antibody recognised beta-FGF and inhibited its mitogenic action on mouse Balb/c cells and bovine endothelial cells in vitro. When examined in vivo, intralesional administration of mouse monoclonal DG-2 antibody significantly inhibited rat chondrosarcoma growth and vascularization. However when the monoclonal DG-2 antibody was administered intraperitoneally or intravenously no attenuation of rat chondrosarcoma tumour vascularization or growth was observed. This report has confirmed the potential effectiveness of anti-beta-FGF antibodies in the regulation of tumour growth. It has also demonstrated that further studies on the pharmacokinetics of administered antibodies and their mode of delivery are required so that the effectiveness of such anti-growth factor immunotherapy can be assured.
Coppola
G
G
Commonwealth Serum Laboratory, Broadmeadows, Victoria, Australia.
Atlas-White
M
M
Katsahambas
S
S
Bertolini
J
J
Hearn
M T
MT
Underwood
J R
JR
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001011:Aorta; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002813:Chondrosarcoma / Q000098:blood supply* / Q000473:pathology* / Q000628:therapy; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000276:immunology* / Q000494:pharmacology* / Q000502:physiology; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D013667:Technetium
D000911:Antibodies, Monoclonal; D016222:Fibroblast Growth Factor 2; D013667:Technetium