Author(s): Davol P, Frackelton AR Jr
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Abstract PURPOSE: 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. MATERIALS AND 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.
This article was published in J Urol
and referenced in Journal of Genetic Syndromes & Gene Therapy