The mitotoxin, basic fibroblast growth factor-saporin, effectively targets human prostatic carcinoma in an animal model.
OBJECTIVE
The antitumor activity of the mitotoxin basic fibroblast growth factor-saporin (bFGF-SAP) against human prostatic carcinoma DU 145 was examined in athymic nude mice. Therapeutic efficacy was evaluated on the basis of dose, route of administration and treatment schedule.


METHODS
Chemical conjugate or recombinant bFGF-SAP (0.02 to 50 micrograms/kg.) was administered by intravenous tail injection, intraperitoneal injection, or local or distal subcutaneous injection beginning 5 days (or 60 to 121 days for large tumor studies) after subcutaneous implantation of DU 145 cells. Tumor growth was monitored as long as 140 days by external caliper measurements.


RESULTS
Recombinant bFGF-SAP, though less cytotoxic than its chemical conjugate form, effectively targeted DU 145 tumors growing as xenografts in nude mice in a dose-dependent manner. Antitumor response to treatment by intravenous, intraperitoneal, or distal subcutaneous injection suggested similar bioavailability of the mitotoxin administered by each route; local subcutaneous injection to the tumor site resulted in statistically better antitumor response. Schedules that included at least 1 bFGF-SAP treatment beyond day 23 increased long-term antitumor efficacy independent of total dose. Moreover, recombinant bFGF-SAP induced dramatic reduction of large, established tumors.


CONCLUSIONS
These studies suggest a therapeutic potential for bFGF receptor-directed toxins in targeting prostate cancer; further, these data suggest that treatment of established tumors (> 3 weeks) results in qualitatively and quantitatively improved tumor responses.
Davol
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Department of Medicine, Roger Williams Medical Center, Providence, Rhode Island 02908, USA.
Frackelton
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AR
D000818:Animals; D003603:Cytotoxins / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006801:Humans; D007267:Injections; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010940:Plant Proteins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
D003603:Cytotoxins; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C078442:basic fibroblast growth factor-saporin mitotoxin, recombinant; D016222:Fibroblast Growth Factor 2; D000076985:Saporins