Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma

Dendritic cells (DCs) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combi ned effectiveness of tumor lysate-pulsed DC immunization and interleukin (I L)-12 administration on the induction of antitumor immunity in a mouse hepa tocellular carcinoma (HCC) model. Mouse DCs were pulsed with lysate of BNL 1ME A.7R.1 (BNL), a BALB/c-derived HCC cell line, and then injected into sy ngeneic mice in combination with systemic administration of IL-12. Lymphocy tes from mice treated with BNL lysate-pulsed DCs and IL-12 showed stronger cytolytic activity and produced higher amounts of IFN-gamma than those from mice treated with BNL lysate-pulsed DCs alone. Although immunization with BNL lysate-pulsed DCs alone did not lead to complete regression of establis hed tumors, it significantly inhibited tumor growth compared with vehicle i njection. Importantly, the combined therapy of BNL lysate-pulsed DCs and IL -12 resulted in tumor rejection or significant inhibition of tumor growth c ompared with mice treated with BNL lysate-pulsed DCs alone. In vivo lymphoc yte depletion experiments demonstrated that this combination was dependent on both CD8(+) and CD4(+) T cells, but not natural killer cells. These resu lts demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DCs against HCC in mice. This combin ation of IL-12 and DCs may be useful for suppressing the growth of residual tumor after primary therapy of human HCC.