Monoclonal antibodies to placental alkaline phosphatase: preclinical evaluation in a human xenograft tumour model of F(ab')2 and Fab fragments.
Six new placental alkaline phosphatase monoclonal antibodies (MAbs) have been evaluated in order to select a potentially clinically useful antibody fragment for use in immunoscintigraphy 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 specific/non-specific ratios at 8 days. In similar fragment biodistribution experiments 3F6 F(ab')2 gave the highest tumour/blood ratio (10) and tumour/organ ratios (19) and the best specific/non-specific localisation. This fragment also showed higher absolute uptake in the tumour than intact antibody, 18.9% and 14.4% 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.
Durbin
H
H
Imperial Cancer Research Fund, London, UK.
Milligan
E M
EM
Mather
S J
SJ
Tucker
D F
DF
Raymond
R
R
Bodmer
W F
WF
D000469:Alkaline Phosphatase / Q000032:analysis* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007527:Isoenzymes / Q000032:analysis* / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D007140:Immunoglobulin Fab Fragments; D007527:Isoenzymes; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental