Antitumor effect of SCV-07 in murine lung and renal cancer models

Abstract

14012 Background: SCV-07 (γ-Glu-Trp) is an immunomodulatory peptide with demonstrated antitumor effects in the murine B16 melanoma model. Herein, the antitumor effects of SCV-07 were evaluated in mice bearing Lewis lung carcinoma (LLC) or renal carcinoma (RenCa) cells. The effect on growth of cultured LLC and RenCa cells was also evaluated to address whether the antitumor effect of SCV-07 is mediated by cytotoxicity. Methods: LLC and RenCa cells were implanted subcutaneously (sc) into the right axillary area of C57BL/6 and Balb/C mice, respectively. SCV-07 was sc administered (at a site different from tumor implantation) once daily at doses of 10 or 20 mg/kg (for LLC) and 5 or 10 mg/kg (for RenCa) for 14 consecutive days. Cisplatin (CDDP, given at 6 mg/kg on days 1, 6, and 12) and cyclophosphamide (CTX, given at 40 mg/kg every other day) were positive controls for LLC and RenCa tumors, respectively. The animals were euthanized on the termination day (day 16 in LLC model, day 17 in RenCa model) and tumors excised and weighed. For the evaluation of cytotoxic effect, LLC or RenCa cells were cultured in 96-well plates with SCV-07 at various concentrations, ranging up to 100 μg/mL, representing the plasma concentrations after effective doses in the mouse models. After 48- (LLC) or 72- (RenCa) hour incubation, inhibitory effects on cell proliferation were determined by the MTT method. Results: In both LLC and RenCa cancer models, SCV-07 treatment led to significant inhibition of tumor growth compared to vehicle control. On the day of study termination, decreases of 16.84% (p<0.05) and 37.45% (p<0.01) in LLC tumor weight were seen after SCV-07 treatment at 10 and 20 mg/kg, respectively, and decreases of 30.02% (p<0.01) and 28.33% (p<0.01) in RenCa tumor weight seen at 5 and 10 mg/kg, respectively. Growth inhibition in the controls were 77.35% (p<0.01) for LLC and 90.12% (p<0.01) for RenCa. In the cultured LLC or RenCa cells, SCV-07 did not inhibit cell proliferation at any tested concentration. Conclusions: Administration of SCV-07 once daily for 14 consecutive days via the sc route is effective against growth of LLC and RenCa tumors. SCV-07 does not induce in vitro cytotoxic effects in cultured LLC and RenCa tumor cells, indicating the antitumor effect of SCV-07 is related to its immunomodulatory actions, rather than cytotoxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration SciClone Pharmaceuticals, Inc. SciClone Pharmaceuticals, Inc SciClone Pharmaceuticals, Inc.