Therapeutic strategy for hepatocellular carcinoma by dendritic cell-based tumor vaccination

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Dendritic cells (DC) are potent antigen-presenting cells that are capable of priming systemic antitumor immune response. Here, we evaluated the combined effectiveness of tumor lysate-pulsed DC immunization and interleukin-12 (IL-12) administration on the induction of antitumor immunity in mouse hepatocellular carcinoma (HCC) model. Mouse DC were pulsed with lysate of BNL 1MB A.7R.1(BNL), a BALB/c-derived HCC cell line, and then injected into syngeneic mice in combination with systemic administration of IL-12. Lymphocytes from mice treated with BNL lysate-pulsed DC and IL-12 showed stronger cytolytic activity and produced higher amounts of IFNγ than those from mice treated with BNL lysate-pulsed DC alone. Although immunization with BNL lysate-pulsed DC alone did not lead to complete regression of established tumors, it significantly inhibited tumor growth compared with vehicle injection. Importantly, the combined therapy of BNL lysate-pulsed DC and IL-12 resulted in tumor rejection or significant inhibition of tumor growth compared with mice treated with BNL lysate-pulsed DC alone. In vivo lymphocyte depletion experiments demonstrated that this combination was dependent on both CD8^+ and CD4^+ T cells, but not NK cells. These results demonstrated that IL-12 administration enhanced the therapeutic effect of immunization of tumor lysate-pulsed DC against HCC in mice. This combination of IL-12 and DC may be useful for suppressing growth of residual tumor after primary therapy of human HCC.