GALACTOSYLATED STREPTAVIDIN FOR IMPROVED CLEARANCE OF BIOTINYLATED INTACT AND F(AB')(2) FRAGMENTS OF AN ANTITUMOR ANTIBODY

Citation
D. Marshall et al., GALACTOSYLATED STREPTAVIDIN FOR IMPROVED CLEARANCE OF BIOTINYLATED INTACT AND F(AB')(2) FRAGMENTS OF AN ANTITUMOR ANTIBODY, British Journal of Cancer, 71(1), 1995, pp. 18-24
Citations number
33
Categorie Soggetti
Oncology
Journal title
ISSN journal
00070920
Volume
71
Issue
1
Year of publication
1995
Pages
18 - 24
Database
ISI
SICI code
0007-0920(1995)71:1<18:GSFICO>2.0.ZU;2-2
Abstract
Persistence of high levels of radiolabelled antibody in the circulatio n is a major limitation of radioimmunotherapy. Biotinylation of the ra diolabelled anti-tumour antibody followed by administration of strepta vidin is known to give much improved tumour to blood ratios as the rad ioantibody is complexed and subsequently cleared via the reticuloendot helial system, although prolonged splenic uptake is a problem. We have investigated the effect on the clearance pattern and tumour localisat ion of a I-125-labelled biotinylated anti-CEA antibody (A5B7) after ad ministration of a galoctosylated form of streptavidin (gal-streptavidi n) in nude mice bearing a human colon carcinoma xenograft. Fifteen min utes to 1 h after gal-streptavidin administration the complexes were c leared via the liver alone (as opposed to liver and spleen after nativ e streptavidin). Twenty-four hours after administration of gal-strepta vidin, the tumour to blood ratio for biotinylated A5B7 IgG increased f rom 2.9 to 13.2 and for biotinylated F(ab')(2) fragments an increase f rom 4.9 to 33.2 was achieved. The reduction in tumour accumulation of F(ab')(2) 24 h after injection of the clearing agent was less than tha t seen with intact antibody. Injection of asialofetuin inhibited clear ance, confirming that removal of the gal-streptavidin-biotinylated ant ibody complexes from the blood was via the asialoglycoprotein receptor on liver hepatocytes. Therefore, galactosylation of the streptavidin clearing agent allows rapid removal of radiolabelled biotinylated anti bodies via the liver asialoglycoprotein receptor, as opposed to the re ticuloendothelial system.