Modern trends in radioimmunotherapy of cancer: pretargeting strategies forthe treatment of ovarian cancer

A review of published data on some of the problems associated in treating c ancer using radioimmunotherapy is presented Potential improvements for this type of therapy using pretargeting strategies are discussed and Preliminar y results on a novel multistep regimen to treat human ovarian cancer are pr esented. A pretargeting strategy using a biotinylated, anti-CA125 monoclona l antibody (MAb) to attract biotinylated long-circulating liposomes to the surface of GA125-expressing ovarian cancer cells, was employed Confocal las er scanning microscopy and florescent labels were used to establish the bio distribution patterns in NIH:OVCAR-3 (CA-125 positive) and SK-OV-3 (CA-125 negative) human ovarian cancer cells. Shedding kinetics of the pretargeted stage were measured using I-125 labeled MAbs. No significant internalizatio n of the MAb used in the pretargeting step was observed by 4 hrs. The antib ody was gradually internalized starting at 6 hrs, and most of the labeled M Ab was detected in cytoplasm by 24 hrs. Shedding and exocytosis of the anti gen-MAb complex was not significant for up to 6-hours following administrat ion of the iodinated MAb. Biotinylated liposomes were shown to specifically target the biotinylated MAb/streptavidin complex on the cell surface. We h ave demonstrated that by a three-step pretargeting approach biotinylated li posomes can he specifically delivered to cells pretargeted with biotinylate d MAb/SAv complex. The slow internalization and shedding properties of the two MAbs are ideal for multistep, pretargeting methods. A successful multis tep linkage was established with the biotinylated MAb B27.1, streptavdin an d biotinylated liposomes to QVCAR-3 cells, but not to SK-OV-3 cells.