Dendritic cell activation by combined exposure to anti‐CD40 plus interleukin (IL)‐12 and IL‐18 efficiently stimulates anti‐tumor immunity

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Abstract:  Despite as yet limited clinical effectiveness, dendritic cell (DC)‐based immunotherapy remains a promising approach for the treatment of cancer, but requires further improvement in its immunostimulatory effectiveness. Potent anti‐tumor immunity often depends on the induction of type 1 (TH1) immune responses. Therefore, we combined different DC maturation stimuli that are known to induce TH1 immunity [anti‐CD40, interleukin (IL)‐12, IL‐18], with the aim to trigger a TH1 driven anti‐tumor CTL response. When compared with untreated DC or DC treated with anti‐CD40 alone, DC matured with anti‐CD40 plus IL‐12 and IL‐18 expressed significantly more IFN‐γ and IL‐12, induced enhanced CD8+ T‐cell proliferation, prolonged synaptic interaction with T cells and increased CD8+ T‐cell‐mediated cytotoxicity. To analyse if these DC are able to induce efficient anti‐tumor immunity, mice carrying a B16‐OVA tumor were treated with tumor antigen (TA)‐loaded DC that had been exposed to anti‐CD40 or to anti‐CD40 plus IL‐12 and IL‐18. Our data show that anti‐CD40 plus IL‐12 and IL‐18 matured DC are superior to controls in retarding tumor growth. These data indicate that maturation of DC with anti‐CD40 plus IL‐12 and IL‐18 potently stimulates the generation of an anti‐tumor immune response and may lead to improved immunotherapeutic capacity of DC vaccination.

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