Monoclonal antibodies to placental alkaline phosphatase: Preclinical evaluation in a human xenograft tumour model of F(ab')2 and Fab fragments

✍ Scribed by H. Durbin; E. M. Milligan; S. J. Mather; D. F. Tucker; R. Raymond; W. F. Bodmer

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: French
• Weight: 531 KB
• Volume: 41
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910410715

✦ Synopsis

Six new placental alkaline phosphatase monoclonal antibodies (MAbs) have been evaluated in order to select a potentially clinically useful antibody fragment for use in immunoxintigraphy or therapy. Initially, 3 antibodies were identified by trial pepsin digestion as likely to give satisfactory F(ab')2 yield. The corresponding intact antibodies were then compared for ability to localise human xenograft tumours in athymic mice. Of the best of these, designated 3F6, F(ab')2 and Fab fragments were then evaluated in similar xenograft experiments. In intact antibody biodistribution comparisons, 3F6 showed good tumour retention and satisfactory specificlnon-specific ratios at 8 days. In similar fragment biodistribution experiments 3F6 F(ab')2 gave the highest tumourlblood ratio (10) and tumourlorgan ratios (19) and the best specificlnon-specific localisation. This fragment also showed higher absolute uptake in the tumour than intact antibody, 18.9% and 14.40/, respectively of the injected dose. As expected, fragments showed much faster blood clearance rates than whole antibody. For Fab the in vivo instability by 6 hr was also demonstrated.