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 recombinant forms of the mitotoxin basic fibroblast growth factor (bFGF) saporin (SAP) and the bFGF receptor-directed immunotoxin 11A8-SAP against 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 micrograms/kg) of chemical conjugate and recombinant bFGF-SAP or 11A8-SAP beginning 5 days after subcutaneous implantation of PA-1 cells was administered by i) weekly injection for 4 weeks, ii) continuous infusion for one week, or iii) daily injection five times a week for 4 weeks.


RESULTS
Weekly injections (31.25 micrograms/kg) of chemical conjugate bFGF-SAP or 11A8-SAP, the 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 recombinant bFGF-SAP administered weekly resulted in mean tumor volumes that were, respectively, 51% or 77% (0.5 microgram/kg) and 42% or 31% (50 micrograms/kg) of controls (day 30). A mean tumor volume of 35% of controls (day 30) and of 49% of controls (day 60) were observed in animals treated by constant infusion of chemical conjugate bFGF-SAP (125 micrograms/kg, total dose). Alternatively, tumors of animals receiving daily injections (125 micrograms/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 therapeutic potential for bFGF-receptor-directed saporin toxins in the treatment of ovarian teratocarcinoma and the importance of frequency of administration in achieving optimal tumor responses.
Davol
P
P
Department of Medicine, Roger Williams Medical Center, Providence, RI 02908, USA.
Beitz
J G
JG
Mohler
M
M
Ying
W
W
Cook
J
J
Lappi
D A
DA
Frackelton
A R
AR
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009699:N-Glycosyl Hydrolases; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010940:Plant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D018243:Teratocarcinoma / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D017468:Receptors, Fibroblast Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins