Dendritic cells transfected with interleukin-12 and pulsed withtumor extract inhibit growth of murine prostatic carcinoma in vivo

BACKGROUND. The induction of anti-tumor immune response by injection of dendritic cells loaded with specific antigen or transduced with genes encoding tumor-specific antigens have been studied in animal models and have shown promising anti-tumor effects. The impact of different routes of administration of dendritic cells on their anti-tumor effects is uncertain. METHODS. We examined the effect of injection of cloned dendritic cells, which were stably transfected with IL-12 and exposed to an extract of murine RM-9 prostate carcinoma cell antigens on tumor growth in vivo. The cloned dendritic cells were injected intramuscularly, subcutaneously, or intraperitoneally into C57BL/6 mice. Seven days later, the mice were inoculated subcutaneously with 100,000 RM-9 cells. The sizes of the resulting tumors were measured every 3 days. RESULTS. Compared with the wild type dendritic cells, the IL-12-transfected dendritic cells delayed tumor engraftment by 7 days (P = 0.04), and reduced tumor growth by up to 80% (P = 0.02). Among the three routes of injection, intramuscular injection was most effective. In contrast to wild type dendritic cells, IL-12-transfected dendritic cells induced infiltration of mononuclear cells into the tumors, and induced apoptosis and necrosis of tumor cells. Injection of IL-12-transfected dendritic cells also significantly delays tumor growth in the preexisting RM-9 tumors. CONCLUSIONS. We conclude that antigen-exposed, IL-12-transfected dendritic cells have potential as an immunotherapy for prostate carcinoma. Routes of administration of dendritic cells are critical for maximal anti-tumor effect.