Flt3-ligand induces transient tumor regression in an ectopic treatment model of major histocompatibility complex-negative prostate cancer

We assessed the in vivo efficacy of Flt3-ligand (Flt3-L) treatment in C57BL /6 mice bearing a well-established MHC class I-negative prostate carcinoma TRAMP-C1, Flt3-L immunotherapy was initiated approximately 30 days after tu mor inoculation, a time when greater than or equal to 80% of the mice had p alpable TRAMP-C1 tumors. Treatment with Flt3-L at 10 mu g/day for 21 consec utive days suppressed TRAMP-C1 tumor growth and induced tumor stabilization (P = 0.0337), Enhanced tumor regression was demonstrated at a higher dose of 30 mu g/day (P < 0.0001), Tumors excised from mice treated with Flt3-L w ere smaller than carrier-treated controls and contained a more pronounced m ixed inflammatory cell infiltrate primarily composed of m Phi. In regressor mice, tumors reappeared at the site of injection when Flt3-L therapy was t erminated. When the experiment was repeated with MHC class I-positive TRAMP -C1 cells, tumor stabilization and/or regression was again observed after t reatment (P < 0.0001); however, once again, tumors reappeared after the ter mination of therapy despite an extended treatment schedule (35 days), MHC c lass I-negative variants were present in tumors isolated from carrier- and Flt3-L-treated mice, and this phenotype could be reversed by IFN-gamma trea tment in vitro, Thus, Flt3-L treatment of mice with preexisting transplanta ble prostate tumors results in tumor regression that is dose-dependent and accompanied by a pronounced mixed-cell inflammatory tumor infiltrate, Howev er, disease relapse was invariably observed after the termination of therap y, which suggests that Flt3-L treatment of advanced MHC- prostate cancers w ill require adjuvant modalities to achieve a durable response.