SAPORIN TOXINS DIRECTED TO BASIC FIBROBLAST GROWTH-FACTOR RECEPTORS EFFECTIVELY TARGET HUMAN OVARIAN TERATOCARCINOMA IN AN ANIMAL-MODEL

Background. The antitumor activity of the chemical conjugate and recom binant forms of the mitotoxin basic fibroblast growth factor (bFGF) sa porin (SAP) and the bFGF receptor-directed immunotoxin 11A8-SAP agains t human ovarian teratocarcinoma PA-1 was examined in athymic nude mice . Alternative administration schedules to prolong therapeutic efficacy were explored. Methods. Intravenous dosing (0.01-125 mu g/kg) of chem ical conjugate and recombinant bFGF-SAP or 11A8-SAP beginning 5 days a fter subcutaneous implantation of PA-1 cells was administered by i) we ekly injection for 4 weeks, ii) continuous infusion for one week, or i ii) daily injection five times a week for 4 weeks. Results. Weekly inj ections (31.25 mu g/kg) of chemical conjugate bFGF-SAP or 11A8-SAP, th e latter of which is 25% the molarity of the former, resulted in mean tumor volumes that were, respectively, 35% or 52% of controls (day 30) and 52% or 76% of controls (day 60), Chemical conjugate or recombinan t bFGF-SAP administered weekly resulted in mean tumor volumes that wer e, respectively, 51% or 77% (0.5 mu/kg) and 42% or 31% (50 mu g/kg) of controls (day 30). A mean tumor volume of 35% of controls (day 30) an d of 49% of controls (day 60) were observed in animals treated by cons tant infusion of chemical conjugate bFGF-SAP (125 mu g/kg, total dose) . Alternatively, tumors of animals receiving daily injections (125 mu g/kg, total dose) exhibited a mean volume of 21% of controls (day 30) and prolonged growth inhibition as demonstrated by a mean tumor volume of 22% of controls (day 60). Conclusions. These studies suggest a the rapeutic potential for bFGF-receptor-directed saporin toxins in the tr eatment of ovarian teratocarcinoma and the importance of frequency of administration in achieving optimal tumor responses.